Affinage

ALOX15

Polyunsaturated fatty acid lipoxygenase ALOX15 · UniProt P16050

Length
662 aa
Mass
74.8 kDa
Annotated
2026-06-09
100 papers in source corpus 51 papers cited in narrative 52 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ALOX15 (15-lipoxygenase-1) is a non-heme iron lipid-peroxidizing enzyme that oxygenates polyunsaturated fatty acids and their esterified derivatives to generate bioactive hydroperoxy and hydroxy lipid mediators governing inflammation resolution, ferroptosis, and tissue homeostasis (PMID:36987924, PMID:10904086, PMID:33177619). The enzyme acts on free arachidonic acid, linoleic acid, EPA, and DHA, with marked substrate preference for n-3 PUFAs, producing 15-HpETE/15-HETE, 13-HODE, 15-HEPE, and DHA-derived 14-/17-HpDHA that serve as precursors for specialized pro-resolving mediators including lipoxins and resolvins (PMID:10904086, PMID:28400162, PMID:33710695, PMID:33177619). Its positional specificity is set by an active-site triad (e.g. Leu353/Ile418, Val418/Val419, Ala404), and during mammalian/primate evolution mutation of these determinants converted the ancestral 12-lipoxygenating enzyme into the 15-lipoxygenating form found in higher primates, optimizing lipoxin synthase activity (PMID:27412860, PMID:25731857, PMID:35531094, PMID:29154477). Beyond free fatty acids, ALOX15 peroxidizes membrane and organelle phospholipids—oxidizing PUFA-phosphatidylethanolamines to drive ferroptotic signals and linoleate within PI3P to suppress LRP5 endosomal recycling and Wnt/β-catenin signaling—and forms a complex with PEBP1 to direct phospholipid peroxidation (PMID:35970840, PMID:32814052, PMID:38492368). Through 15-HpETE generation it executes ferroptotic cell death programs, in cardiomyocytes by promoting RNF34-dependent Pgc1α degradation and impaired mitochondrial biogenesis, an activity antagonized by GPX4 (PMID:36987924, PMID:27634046). ALOX15 sits downstream of multiple transcriptional and metabolic ferroptosis axes including SSAT1, p53/DHODH, and Bmal1/EZH2/EBF3, while its own transcription is repressed by the NuRD (MTA1/HDAC1) complex and GATA-6 in cancer cells, activated by an SPI1-binding promoter SNP and LXR in macrophages, and tuned by histone acetylation (PMID:16320347, PMID:19198625, PMID:35090880, PMID:36942513, PMID:37271497, PMID:33177619). Physiologically, ALOX15-derived mediators drive resolution of inflammation in vagal neural-immune circuits, synaptic plasticity and memory, intestinal barrier integrity, and skin and colitis resolution, while its peroxidation activity also contributes to NAFLD, alcoholic liver injury, neuropathic pain, autoimmune diabetes, and reduced bone mineral density (PMID:14716014, PMID:35622894, PMID:28181190, PMID:29702245, PMID:23818745, PMID:30130298).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2000 High

    Established that ALOX15 is not merely a metabolic enzyme but a pro-apoptotic effector in colon cancer cells via its linoleic acid product 13-S-HODE, answering whether its catalytic output has direct cell-fate consequences.

    Evidence Enzyme activity assays, 13-S-HODE quantification, inhibitor plus metabolite rescue in RKO and HT-29 colorectal cancer cells

    PMID:10904086

    Open questions at the time
    • Downstream apoptotic effectors of 13-S-HODE not defined
    • Does not address phospholipid substrates or in vivo relevance
  2. 2004 High

    Extended ALOX15 function beyond cancer to skeletal physiology, showing the enzyme negatively regulates peak bone mineral density and is a pharmacological target for bone strength.

    Evidence Genetic mapping, Alox15 knockout crossbreeding, and inhibitor treatment in two rodent osteoporosis models

    PMID:14716014

    Open questions at the time
    • Lipid mediator linking ALOX15 to osteoblast/osteoclast biology not identified
    • Cell type responsible not pinpointed
  3. 2006 High

    Defined cis- and trans-acting transcriptional control of ALOX15, showing a promoter SNP creates an SPI1 site driving macrophage-selective expression, and GATA-6 contributes to silencing in cancer.

    Evidence Luciferase assays, EMSA, promoter mutagenesis, primary human macrophage qRT-PCR; GATA-6 siRNA in Caco-2/HCT-116 cells

    PMID:16320347 PMID:17167069

    Open questions at the time
    • How SPI1 and repressors are coordinated across cell types unresolved
    • GATA-6 effect insufficient alone
  4. 2009 High

    Identified the chromatin machinery silencing ALOX15 in cancer, placing the NuRD complex (MTA1/HDAC1) on the promoter and explaining HDAC-inhibitor reactivation.

    Evidence siRNA knockdown of HDAC1/MTA1, ChIP, luciferase reporters, depsipeptide in colon cancer cells

    PMID:19198625

    Open questions at the time
    • Signals recruiting NuRD to the promoter not defined
    • Generality beyond colon cancer untested
  5. 2016 High

    Resolved the structural basis and evolutionary logic of ALOX15 reaction specificity, showing triad residues convert 12- to 15-lipoxygenation and optimize lipoxin synthesis in higher primates.

    Evidence Ortholog cloning/expression, lipoxin synthase assays, site-directed mutagenesis, QM/MM and MD simulations across many species

    PMID:25731857 PMID:27412860 PMID:29154477 PMID:35531094

    Open questions at the time
    • Physiological consequence of the evolutionary switch in vivo not directly tested at this stage
    • Specificity with esterified substrates less fully characterized
  6. 2017 High

    Broadened the substrate scope, showing ALOX15 prefers EPA and DHA over arachidonic acid and produces dual-specificity SPM precursors, reframing it as a key generator of n-3-derived resolution mediators.

    Evidence Recombinant expression of eight mammalian orthologs with multiple PUFA substrates and product characterization

    PMID:28400162

    Open questions at the time
    • In vivo substrate selection under physiological PUFA ratios not established
    • Tissue-specific product spectra unknown
  7. 2017 High

    Demonstrated CNS roles for ALOX15, localizing it to prefrontal cortical dendrites and showing its DHA-to-resolvin D1 conversion is required for synaptic plasticity and working memory.

    Evidence Immuno-EM, LC-MS for resolvin D1, inhibition/antisense knockdown, LTP recording, and T-maze testing in rat

    PMID:28181190

    Open questions at the time
    • Receptor for resolvin D1 mediating LTP not identified
    • Human relevance untested
  8. 2020 High

    Established that ALOX15 oxidizes esterified lipids in trafficking compartments, peroxidizing PI3P-linoleate to block LRP5 recycling and suppress Wnt/β-catenin signaling in colon.

    Evidence Transgenic and Apc/azoxymethane mouse models, in vitro lipid peroxidation, PI3P-SNX17-LRP5 interaction and endosomal trafficking assays

    PMID:32814052

    Open questions at the time
    • Whether PI3P peroxidation occurs in non-intestinal tissues unknown
    • Selectivity for PI3P vs other phosphoinositides not fully mapped
  9. 2020 High

    Connected ALOX15 expression to macrophage resolution programs, showing efferocytosis potentiates ALOX15 via LXR to enhance SPM precursor synthesis.

    Evidence Primary human macrophage efferocytosis, transcriptomics, LXR agonist, NPC1 inhibition, LXR siRNA, lipidomics

    PMID:33177619

    Open questions at the time
    • Direct LXR binding to the ALOX15 promoter not shown
    • In vivo contribution to resolution not measured here
  10. 2022 High

    Positioned ALOX15 as the executioner of ischemic phospholipid peroxidation and ferroptotic signaling in cardiomyocytes, identifying its preferred PE-PUFA substrates.

    Evidence Multi-omics and chemogenetic approaches in animal and in vitro cardiac models

    PMID:35970840

    Open questions at the time
    • Specific oxidized PE species driving ferroptosis not exhaustively defined
    • Relationship to GPX4 antagonism in heart not quantified
  11. 2022 High

    Defined ALOX15 as a required effector in the neural-immune inflammatory reflex, linking vagus nerve stimulation to SPM-driven resolution.

    Evidence Electrical VNS in zymosan peritonitis with metabololipidomics and Alox15-deficient mouse comparison

    PMID:35622894

    Open questions at the time
    • Cellular source of ALOX15 in the reflex not pinpointed
    • Receptors transducing the SPM signal not defined
  12. 2023 High

    Defined the cardiac ferroptosis mechanism downstream of ALOX15, showing 15-HpETE drives RNF34-dependent Pgc1α degradation and mitochondrial collapse during I/R injury.

    Evidence Cardiac-specific knockout, metabolomics, protein interaction assays, and ML351 inhibition in mice

    PMID:36987924

    Open questions at the time
    • How 15-HpETE engages the Pgc1α-RNF34 interaction biochemically unresolved
    • Whether the same axis operates in non-cardiac ferroptosis untested
  13. 2024 High

    Identified a direct protein partner, showing PEBP1 complexes with ALOX15 to direct membrane phospholipid peroxidation and impair macrophage phagocytosis under stress.

    Evidence Co-IP, microscale thermophoresis, docking, phospholipidomics, and phagocytosis assays in a breast cancer model

    PMID:38492368

    Open questions at the time
    • Structural basis of the ALOX15-PEBP1 interface not solved
    • Whether PEBP1 redirects positional specificity unknown
  14. 2024 Medium

    Mapped the transcriptional ferroptosis circuitry feeding ALOX15, placing it downstream of Bmal1/EZH2/EBF3, p53/DHODH, SSAT1, and SREBF2/PER1 regulatory axes.

    Evidence ChIP, knockdown/overexpression, and ferroptosis assays across AML, neuronal, granulosa, and SCI models

    PMID:35090880 PMID:36942513 PMID:37271497 PMID:38653359

    Open questions at the time
    • Direct vs indirect promoter regulation by several factors not uniformly confirmed
    • PER1/SREBF2 axis rests on Low-confidence binding evidence

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how ALOX15 selects between resolution-promoting (SPM precursor) and cytotoxic (ferroptotic phospholipid peroxidation) outputs in a given cell, and what governs the switch between these opposing functions.
  • No unifying model linking substrate channeling, PEBP1 complex, and product fate
  • Determinants of free-fatty-acid vs esterified-lipid oxidation in vivo unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 7 GO:0140096 catalytic activity, acting on a protein 3 GO:0008289 lipid binding 2 GO:0016740 transferase activity 1
Localization
GO:0005886 plasma membrane 2 GO:0005768 endosome 1 GO:0005829 cytosol 1
Pathway
R-HSA-5357801 Programmed Cell Death 5 R-HSA-1430728 Metabolism 4 R-HSA-168256 Immune System 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-162582 Signal Transduction 2
Partners
GPX4LRP5PEBP1RNF34SNX17

Evidence

Reading pass · 52 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2023 ALOX15 catalyzes conversion of arachidonic acid to 15-HpETE, which promotes cardiomyocyte ferroptosis by binding Pgc1α to the ubiquitin ligase RNF34, leading to ubiquitin-dependent Pgc1α degradation, attenuated mitochondrial biogenesis, and abnormal mitochondrial morphology. Myocardial-specific knockout of Alox15 alleviated I/R injury; ML351 (specific ALOX15 inhibitor) rescued cardiac function. Mouse cardiac-specific knockout, metabolomics, loss/gain-of-function experiments, protein interaction assays, pharmacological inhibition (ML351) Circulation High 36987924
2022 ALOX15 is the primary mediator of ischemia-provoked phospholipid peroxidation in cardiomyocytes, specifically oxidizing PUFA-containing phosphatidylethanolamines to generate ferroptotic lipid signals; identified by multi-omics and confirmed by chemogenetic approaches. Multi-omics analysis, chemogenetic approaches, animal and in vitro models Signal transduction and targeted therapy High 35970840
2004 Alox15 (12/15-lipoxygenase) negatively regulates peak bone mineral density in mice; crossbreeding with Alox15 knockout mice confirmed this skeletal role, and pharmacological inhibitors of the enzyme improved bone density and strength in two rodent osteoporosis models. Genetic mapping, Alox15 knockout mouse crossbreeding, pharmacological inhibition in rodent models Science (New York, N.Y.) High 14716014
2000 15-LOX-1 (ALOX15) enzymatic activity in colorectal cancer cells metabolizes linoleic acid to 13-S-HODE, which induces apoptosis; NSAIDs (sulindac, NS-398) increase 15-LOX-1 protein expression and enzymatic activity, and pharmacological inhibition of 15-LOX-1 blocked NSAID-induced apoptosis, which was rescued by exogenous 13-S-HODE but not linoleic acid. 15-LOX-1 protein expression assay, enzymatic activity measurement, 13-S-HODE quantification, pharmacological inhibition (caffeic acid), exogenous metabolite rescue in colorectal cancer cell lines (RKO, HT-29) Journal of the National Cancer Institute High 10904086
2016 Evolutionary alteration of ALOX15 reaction specificity—from 12-lipoxygenating in lower primates to 15-lipoxygenating in higher primates (humans, chimpanzees, orangutans)—optimizes lipoxin synthase activity; 15-lipoxygenating ALOX15 variants have >5-fold higher lipoxin synthase activity than 12-lipoxygenating variants. Triad residues (e.g., Ile418) are key specificity determinants confirmed by mutagenesis and QM/MM calculations. Cloning and expression of multiple ALOX15 orthologs, lipoxin synthase activity assays, site-directed mutagenesis (humIle418Ala), QM/MM energy calculations, molecular dynamics simulations Proceedings of the National Academy of Sciences of the United States of America High 27412860
2017 Mammalian ALOX15 orthologs exhibit pronounced dual positional specificity with DHA, forming similar amounts of 14- and 17-HpDHA; ALOX15 orthologs prefer DHA and EPA over arachidonic acid when equimolar amounts are supplied. The reaction specificity strongly depends on fatty acid substrate chemistry. Recombinant expression of eight mammalian ALOX15 orthologs as his-tag fusion proteins, substrate oxygenation assays with multiple PUFAs (AA, EPA, DHA), product characterization Biochimica et biophysica acta. Molecular and cell biology of lipids High 28400162
2015 Mutagenesis of triad determinants (Leu353, Ile593, Ala404) in rat Alox15 alters reaction specificity with free fatty acids and complex ester lipids; Leu353Phe mutation converts the enzyme from 12-lipoxygenating to 15-lipoxygenating activity. The Ala404Gly exchange induced subtle alterations in enantioselectivity, partially supporting the Coffa/Brash concept. Recombinant rat Alox15 expression (prokaryotic and eukaryotic systems), multiple site-directed mutagenesis, enzymatic oxygenation assays with free fatty acids and phospholipid substrates (biomembranes, HDL) Archives of biochemistry and biophysics High 25731857
2020 15-LOX-1 (ALOX15) peroxidates linoleic acid in phosphatidylinositol-3-phosphates (PI3P_LA → PI3P_13-HODE), which decreases PI3P binding to SNX17 and LRP5, inhibits LRP5 recycling from endosomes to the plasma membrane, and promotes LRP5 lysosomal degradation, thereby suppressing Wnt/β-catenin signaling and colorectal carcinogenesis. Transgenic mouse intestinal expression of ALOX15, Apc-mutant mouse model, azoxymethane CRC model, in vitro reconstitution of lipid peroxidation, PI3P-SNX17-LRP5 interaction assays, endosomal trafficking assays Cell reports High 32814052
2006 A C-to-T SNP at position c.-292 in the ALOX15 promoter creates a novel binding site for transcription factor SPI1 (PU.1); alleles carrying c.-292T transcribe twice as efficiently as c.-292C alleles in macrophages that constitutively express SPI1, but not in lung epithelial cells lacking SPI1. EMSA confirmed selective SPI1 binding to the mutant promoter; primary macrophages from heterozygous carriers expressed 3× more ALOX15 mRNA. Luciferase transcription assays, EMSA (electrophoretic mobility shift assay), SPI1 core-binding site mutagenesis, qRT-PCR in primary human macrophages from genotyped donors Human mutation High 16320347
2009 ALOX15 transcription in colon cancer cells is suppressed by recruitment of the NuRD repressor complex (containing MTA1 and HDAC1) to the region -120 to -391 of the 15-LOX-1 promoter; HDAC inhibitors (depsipeptide) reduce NuRD recruitment and reactivate 15-LOX-1 transcription. MTA1 expression in colorectal cancer is negatively correlated with 15-LOX-1 expression. siRNA knockdown of HDAC1, HDAC2, MTA1; luciferase reporter assays with 15-LOX-1 promoter constructs; chromatin immunoprecipitation; HDAC inhibitor treatment (depsipeptide) Oncogene High 19198625
2006 GATA-6 transcription factor overexpression contributes to 15-LOX-1 transcriptional silencing in colon cancer cells; GATA-6 siRNA knockdown alone is insufficient but significantly contributes to restoring 15-LOX-1 expression and inducing apoptosis when combined with NSAID (NS-398) or HDAC inhibitor (sodium butyrate) treatment. GATA-6 siRNA transfection in Caco-2 and HCT-116 cells, 15-LOX-1 expression measurement, apoptosis assays, NS-398 and sodium butyrate treatments, paired human colorectal cancer tissue analysis FASEB journal Medium 17167069
2007 A coding SNP T560M in ALOX15 results in a near-null variant with 20-fold reduction in catalytic activity compared to wild-type enzyme, as demonstrated by in vitro enzymatic assays. ALOX15 resequencing, in vitro enzymatic activity assay of T560M vs T560 variants, genotyping in population studies Atherosclerosis Medium 17959182
2010 ALOX15 (15-lipoxygenase) is present in sperm cytoplasmic droplets (CDs) and required for normal epididymal sperm maturation; Alox15 knockout male mice have significantly more spermatozoa with retained CDs containing intact mitochondria in both caput and cauda epididymidis, compared to wild-type where CDs contain only hollow membrane vesicles with no intact mitochondria. Alox15 knockout mouse analysis, differential interference contrast microscopy (DIC), transmission electron microscopy (TEM) of epididymal sperm from Alox15 vs wild-type males Cell and tissue research Medium 20449608
2016 Systemic inactivation of the Alox15 gene normalizes reduced fertility and sperm motility in male mice heterozygous for catalytically inactive Gpx4 (Sec46Ala-Gpx4+/-); Alox15 deficiency rescues sperm midpiece structural alterations and motility defects, demonstrating that ALOX15-mediated lipid oxidation is functionally antagonized by GPX4 in male reproductive function. Genetic cross of Gpx4 knock-in mice with Alox15 knockout mice, fertility assessment, sperm motility analysis, ultrastructural analysis The Journal of biological chemistry High 27634046
2014 Alox15 deficiency does NOT rescue homozygous Gpx4 catalytically inactive knock-in mice (Sec46Ala-Gpx4+/+) from embryonic lethality (E6-7), indicating that Alox15-mediated lipid peroxidation is not the primary cause of embryonic lethality in GPX4-null mice. Genetic cross of Sec46Ala-Gpx4 knock-in mice with Alox15 knockout mice, embryonic viability assessment, embryo staging Antioxidants & redox signaling High 25313597
2010 Alox15 gene disruption in ApoE-/- mice protects against nonalcoholic fatty liver disease; Alox15 deficiency reduces hepatic steatosis, inflammation, macrophage infiltration, attenuates glucose intolerance and insulin resistance, upregulates insulin receptor substrate-2, and exerts opposite effects on hepatic JNK and AMPK phosphorylation. Hepatocytes from Alox15-deficient mice are less vulnerable to TNFα-induced programmed cell death. ApoE-/-/Alox15-/- double knockout mice, hepatocyte isolation and TNFα challenge, JNK and AMPK phosphorylation assays, glucose/insulin tolerance tests, gene expression analysis Hepatology (Baltimore, Md.) High 20967760
2013 12/15-lipoxygenase (Alox15) is expressed in macrophages but not B and T cells of NOD mice; deletion of Alox15 decreases proinflammatory cytokine expression in macrophages, splenocytes from NOD-Alox15(null) mice cannot transfer diabetes in adoptive transfer, and absence of Alox15 maintains islet health and beta cell mass, demonstrating that Alox15 regulates macrophage inflammation driving autoimmunity in type 1 diabetes. qRT-PCR cell-type expression analysis, adoptive transfer model, Western blotting, beta cell mass quantification in NOD-Alox15(null) mice PloS one Medium 23437231
2022 Vagus nerve stimulation (VNS) promotes resolution of inflammation and increases specialized proresolving mediators (SPMs) from DHA and n-3 DPA metabolomes; this VNS-mediated shift toward proresolving lipid mediator profile is inverted in Alox15-deficient mice, establishing Alox15 as a required effector in the neural-immune inflammatory reflex pathway. Electrical VNS in zymosan-induced peritonitis mouse model, lipid mediator metabololipidomics, Alox15-deficient mouse comparison, α7nAChR-deficient mouse comparison Proceedings of the National Academy of Sciences of the United States of America High 35622894
2021 Alox15-derived 15-HEPE (15-hydroxy eicosapentaenoic acid) is the anti-colitis mediator responsible for the protective effect of increased n-3 PUFA in fat1 transgenic mice; Alox15 gene inactivation in fat1 mice abolishes their protection from DSS- and TNBS-induced colitis, and intraperitoneal 15S-HEPE administration protects wild-type mice from colitis. fat1×Alox15-/- genetic cross, DSS and TNBS colitis models, Alox15 lipid metabolite analysis, 15S-HEPE intraperitoneal treatment in wild-type mice FASEB journal High 33710695
2018 Alox15/ALOX15B are expressed in cardiac fibroblasts; hypoxia significantly increases ALOX15 and ALOX15B gene and protein expression in fibroblasts from failing human hearts. Conditioned medium from hypoxic fibroblasts decreases beating frequency of human iPSC-derived cardiomyocytes in an ALOX15-dependent manner (effect blocked by ALOX15 inhibition). Gene expression in isolated cardiac fibroblasts under hypoxia vs normoxia, 15-HETE measurement, paracrine co-culture with iPSC-derived cardiomyocytes, calcium imaging, ALOX15 inhibition PloS one Medium 30138423
2017 ALOX15 (Alox15) is expressed in rat brain, with highest mRNA and protein expression in the prefrontal cortex; it is localized to dendrites by immuno-electron microscopy. Alox15 inhibition or antisense knockdown in prefrontal cortex significantly decreased resolvin D1 levels, blocked hippocampo-prefrontal cortex long-term potentiation, and increased errors in T-maze spatial working memory, establishing Alox15 as mediating DHA-to-resolvin D1 conversion required for synaptic plasticity and memory. RT-PCR, Western blot, immunohistochemistry, immuno-electron microscopy, LC-MS for resolvin D1, pharmacological inhibition and antisense knockdown of Alox15 in prefrontal cortex, LTP recording, T-maze behavioral test Molecular neurobiology High 28181190
2017 Alox15 expression in neuroblastoma cells is regulated by histone acetylation; HDAC inhibitors (TSA, sodium butyrate, Class I inhibitors MS-275 and depsipeptide) upregulate Alox15 mRNA. The p300 histone acetyltransferase (HAT) inhibitor C646 modulates TSA- and retinoic acid-induced Alox15 upregulation, indicating p300 HAT activity is required for Alox15 transcriptional induction during neuronal differentiation. HDAC inhibitor treatment of SH-SY5Y cells, Class I-specific HDAC inhibitors, p300 HAT inhibitor (C646) co-treatment, retinoic acid differentiation, qRT-PCR, primary murine cortical neuron developmental expression Neurochemical research Medium 29235036
2017 ALOX15 upregulation leads to hepatic overproduction of 13-HODE, which induces oxidative stress, ER stress, lipid metabolic disorder, and apoptosis; ALOX15 knockout prevents alcohol-induced liver damage through attenuation of these pathways. Linoleic acid (not ethanol or acetaldehyde) induces ALOX15 expression in hepatocytes. Chronic alcohol feeding mouse model, ALOX15 knockout mice, ALOX15 inhibitor (PD146176) treatment, 13-HODE exposure to Hepa-1c1c7 cells, oxidative stress, ER stress, and apoptosis markers Scientific reports High 28827690
2022 SSAT1 overexpression upregulates ALOX15 expression in neurons and promotes ferroptosis by decreasing GPX4 and SLC7A11 levels; SSAT1 knockdown downregulates ALOX15 and reduces lipid hydroperoxide production. ALOX15 inhibitor PD146176 partially reverses SSAT1 upregulation-induced ferroptosis, placing ALOX15 downstream of SSAT1 in neuronal ferroptosis signaling. SSAT1 knockdown/overexpression in primary cortical neurons and tMCAO/R mouse model, ALOX15 inhibitor (PD146176) treatment, iron/ROS/lipid peroxide measurements, GPX4/SLC7A11 protein levels Neuroscience Medium 35090880
2023 DHODH inhibits neuronal ferroptosis after spinal cord injury via the P53/ALOX15 signaling pathway: DHODH inhibits P53 expression, which in turn suppresses ALOX15 expression, reducing lipid peroxidation and ferroptosis. Rat SCI model, erastin-induced PC12 cells, DHODH overexpression/inhibition, P53 and ALOX15 expression analysis, lipid peroxide and mitochondrial damage measurement CNS neuroscience & therapeutics Medium 36942513
2020 Efferocytosis by alternatively activated macrophages potentiates ALOX15 expression through LXR activation; AC uptake upregulates LXR-dependent gene expression and suppresses SREBP-2-dependent gene expression via NPC1-mediated sterol transport. LXRα/β silencing attenuates this ALOX15 potentiation. Enhanced ALOX15 expression increases capacity to synthesize SPM precursors 15-HETE and 17-HDHA and resolvin D5. Apoptotic cell efferocytosis in primary human macrophages, global transcriptome analysis, LXR agonist (T0901317), NPC1 inhibition, LXRα/β siRNA silencing, lipidomics (15-HETE, 17-HDHA, resolvin D5 measurement) Cell death and differentiation High 33177619
2008 Alox15 is induced in the small and large intestine and liver of iron-deficient rats; increased Alox15 protein leads to production of 12-HETE, 13-HODE, and 13-HOTE (confirmed by HPLC), representing a perturbation of intestinal lipid metabolism driven by Alox15 activity during iron deficiency. Gene chip studies in iron-deficient and Belgrade rats, TaqMan qRT-PCR, polyclonal antibody immunodetection, HPLC lipid analysis American journal of physiology. Gastrointestinal and liver physiology Medium 18258795
2010 Selenoprotein P (SelP) has in vitro lipid hydroperoxidase activity against 15-HpETE (the ALOX15 product), attenuates 15-HpETE oxidation in cellular assays, and reduces oxidative damage in a transcellular assay when 15-LOX-1 is metabolically active, identifying SelP as an antioxidant counterpart to 15-LOX-1. In vitro lipid hydroperoxidase assay with recombinant SelP and 15-HpETE, cellular 15-HpETE oxidation assay, transcellular assay with metabolically active 15-LOX-1 Prostaglandins, leukotrienes, and essential fatty acids Medium 20826080
2022 The ALOX15 specificity switch during mammalian evolution follows a Triad Concept: >90% of mammalian ALOX15 orthologs catalyze 12-lipoxygenation; mammals ranked above gibbons express 15-lipoxygenating orthologs; triad determinant mutagenesis studies on 44 novel orthologs confirmed the specificity predictions. Gibbon ALOX15 represents a transition enzyme with dual specificity. Sequence analysis of 152 mammalian ALOX15 orthologs, expression of 44 novel recombinant ALOX15 orthologs, enzymatic specificity assays, extensive mutagenesis of triad determinants Frontiers in cell and developmental biology High 35531094
2017 Mutagenesis of porcine ALOX15 Val418 and Val419 sequence determinants converts the enzyme from 12-lipoxygenating to 15-lipoxygenating activity; QM/MM calculations showed that the Val418Ile+Val419Met double mutant has a 6.0 kcal/mol higher barrier for 12-lipoxygenation than 15-lipoxygenation, explaining the specificity switch by altering enzyme-substrate complex geometry. Site-directed mutagenesis of porcine ALOX15 crystal structure, molecular docking, MD simulations, QM/MM calculations Chemistry (Weinheim an der Bergstrasse, Germany) High 29154477
2020 Gln596 of mammalian ALOX15 does not directly interact with the carboxylate of arachidonic acid; instead, mutations at Gln596 destabilize secondary/tertiary structure and impair allosteric enzyme properties by disturbing the electrostatic interaction network. MD simulations suggest dimer interface geometry depends on substrate bound in the active site, and Gln596Ala impairs allosteric communication between monomers. Site-directed mutagenesis of rabbit and human ALOX15 at Gln596, structural stability assays, steady-state kinetics, MD simulations, substrate docking Biochimica et biophysica acta. Molecular and cell biology of lipids Medium 32151768
2022 N-substituted 5-(1H-indol-2-yl)-2-methoxyanilines are allosteric inhibitors of the linoleate oxygenase activity of rabbit and human ALOX15; they selectively inhibit oxygenation of linoleic acid at submicromolar concentrations without affecting arachidonic acid oxygenation. Steady-state kinetics, mutagenesis, and MD simulations of the ALOX15 dimer model indicate binding at the active site of one monomer induces conformational changes in the other monomer, compromising productive linoleic acid-enzyme complex formation. In vitro enzymatic assays (steady-state kinetics), site-directed mutagenesis, MD simulations of ALOX15 dimer model, synthesis of inhibitor series Journal of medicinal chemistry High 35073698
2021 Rabbit ALOX15 and human ALOX15B exist as two conformers with distinct electrophoretic mobilities in native PAGE; MD simulations and mutagenesis suggest motional flexibility in aqueous solution impacting enzymatic properties, consistent with a dynamic monomer-dimer equilibrium with substrate-dependent conformational heterogeneity. Native polyacrylamide electrophoresis, in silico docking, MD simulations, site-directed mutagenesis, kinetic measurements International journal of molecular sciences Medium 33807076
2004 15-LOX-1 overexpression in HCT-116 colon cancer cells induces ERK1/2 phosphorylation, decreases p21 (Cip/WAF1) expression, and increases cell growth; its product 13-S-HODE reverses NaBT-induced p21 expression. LOX inhibitor (NDGA) decreased ERK1/2 phosphorylation and increased p21 expression in 15-LOX-1 overexpressing cells. 15-LOX-1 transfection in HCT-116 cells, ERK1/2 phosphorylation assay, p21 expression analysis, NDGA inhibitor treatment, sodium butyrate treatment Prostaglandins & other lipid mediators Medium 15165036
2017 Intestinally-targeted transgenic expression of ALOX15 in mice inhibits DSS-induced colitis from promoting azoxymethane-induced colorectal tumorigenesis; ALOX15 suppresses TNF-α, IL-1β/NF-κB, and IL-6/STAT3 inflammatory signaling pathways that drive colorectal cancer promotion. ALOX15 intestinal transgenic mouse model, DSS-colitis model, azoxymethane carcinogen model, cytokine/signaling pathway analysis Prostaglandins & other lipid mediators Medium 28089732
2018 Systemic Alox15 deficiency in female mice protects against DSS-induced colitis by sustaining expression of the tight junction protein ZO-1 and maintaining intestinal epithelial barrier function; exogenous 12S-HETE (the major mouse Alox15 product) enantioselectively compromises transepithelial electric resistance in colon epithelial cells. Transgenic overexpression of human ALOX15 intensified inflammatory symptoms. Alox15-/- mouse DSS colitis model, 12S-HETE epithelial barrier assay (transepithelial electric resistance), ZO-1 immunostaining, ALOX15 transgenic overexpression, 12-HETE in vivo quantification Biochimica et biophysica acta. Molecular and cell biology of lipids High 29702245
2013 IFN-γ suppresses ALOX15 expression during resolution of PMA-induced skin inflammation; neutralization of endogenous IFN-γ boosts ALOX15 expression and LXA4 production, promoting proresolution effects. Exogenous LXA4 (an ALOX15 product) recapitulates the proresolution effect of IFN-γ neutralization. In vivo PMA-induced skin inflammation model in mice, IFN-γ neutralizing antibody, ALOX15 expression analysis, exogenous LXA4 treatment Mediators of inflammation Medium 23818745
2018 Spinal TLR4 activation by intrathecal KLA increases 15-LOX-1 expression specifically in microglia (not astrocytes) and increases 12-lipoxygenase-mediated hepoxilin production in lumbar spinal cord; intrathecal pretreatment with 15-LOX-1-specific inhibitors (ML127, ML351, CDC) or a selective antibody against rat 15-LOX-1 completely abrogated TLR4-induced tactile allodynia, establishing spinal microglial ALOX15 as mediating TLR4-dependent neuropathic pain. Intrathecal KLA administration, lipidomics of spinal cord, primary spinal microglia/astrocyte cultures, selective ALOX15 antibody neutralization, ML127/ML351/CDC pharmacological inhibition, HEK-293T heterologous expression of rat 15-LOX-1 for inhibitor testing Pain High 30130298
2014 15-LOX-1 re-expression in colon cancer cells (HCT116, HT29LMM, LoVo) under hypoxia inhibits HIF-1α protein expression and stability, reduces VEGF expression, angiogenesis, cancer cell migration, invasion, and survival under hypoxia, demonstrating that 15-LOX-1 suppresses hypoxia-driven metastatic mechanisms. 15-LOX-1 re-expression in three colon cancer cell lines under hypoxia, HIF-1α protein stability assay, VEGF ELISA, angiogenesis assay, migration and invasion assays Cancer medicine Medium 24634093
2024 FGF21 deficiency results in abnormal activation of the ALOX15/15-HETE pathway, triggering innate immunity-dominated pro-inflammatory responses in liver grafts; pharmacological recombinant FGF21 administration protects against hepatic I/R injury and suppresses the ALOX15/15-HETE axis, particularly in steatotic livers. Hepatic I/R injury and orthotopic LT mouse models, FGF21 KO mice, recombinant FGF21 treatment, ALOX15/15-HETE pathway analysis, arachidonic acid metabolomics Nature communications Medium 39362839
2024 PEBP1 forms a complex with ALOX15 in macrophages under psychological stress, mediating membrane phospholipid peroxidation that compromises macrophage phagocytic capacity; inhibition of the ALOX15/PEBP1 interaction (e.g., by isochlorogenic acid C, ICAC) attenuates phospholipid peroxidation and restores phagocytic function in the tumor microenvironment. Co-immunoprecipitation, microscale thermophoresis (MST) binding assay, molecular docking, LC-MS/MS phospholipidomics, flow cytometry phagocytosis assay, in vivo breast cancer model Phytomedicine High 38492368
2021 Alox15 deficiency in chronic kidney disease (5/6 nephrectomy) mice improves renal function and inhibits interstitial fibrosis; mediator lipidomics revealed significantly higher PGD2 in Alox15-/- CKD kidneys, and exogenous PGD2 dose-dependently suppresses TGF-β1-induced type I collagen and αSMA in renal epithelial cells, suggesting ALOX15 suppresses PGD2, which is anti-fibrotic. Alox15-/- mouse 5/6 nephrectomy CKD model, mediator lipidomics, PGD2 treatment of NRK-52E and HK-2 cells, fibrosis marker quantification Clinical and experimental nephrology Medium 33595729
2023 Bmal1 inhibits RSL3-induced ferroptosis in AML cells by recruiting EZH2 to the EBF3 promoter to enhance its methylation and suppress EBF3 expression; EBF3 binds to the ALOX15 promoter to enhance ALOX15 expression, promoting ferroptosis. Thus ALOX15 is downstream of the Bmal1/EZH2/EBF3 axis in ferroptosis regulation in AML. Bmal1/EBF3 knockdown/overexpression in HL-60 and NB4 cells, EZH2 ChIP at EBF3 promoter, EBF3 ChIP at ALOX15 promoter, subcutaneous AML xenograft model, ferroptosis assays (MDA, GSH, lipid peroxidation, iron) Cancer science Medium 37271497
2025 ALOX15 promotes lipid accumulation in hepatocytes through the PPARγ/CD36 pathway; ALOX15 overexpression increases intracellular fatty acid uptake and lipotoxicity, which are reversed by PPARγ antagonist (GW9662) or CD36 inhibitor. GLP-1 receptor agonist liraglutide improves hepatic lipid accumulation in MASLD mice by suppressing the ALOX15/PPARγ/CD36 pathway. ALOX15 lentiviral overexpression and siRNA KD in HepG2 cells, palmitic acid lipotoxicity model, PPARγ antagonist (GW9662) and CD36 inhibitor treatment, ALOX15 metabolomics (12-HpETE, 15-HpETE), transcriptomics, HFD/STZ mouse model Antioxidants & redox signaling Medium 39815992
2024 Alpha-tocopherol (Vitamin E) downregulates Alox15 expression and inhibits ferroptosis after spinal cord injury; mutation of the 87th residue of Alox15 weakens the inhibitory effect of alpha-tocopherol on Alox15, identifying this residue as important for the alpha-tocopherol/Alox15 interaction. SCI rat model, alpha-tocopherol treatment, Alox15 expression analysis, Alox15 87th residue mutation, immunofluorescence localization, in vitro ROS and lipid peroxidation assays Biomedicine & pharmacotherapy Medium 38754264
2024 Lactate-induced HIF1A transcriptional activation (via histone lactylation of the HIF1A promoter) exacerbates severe acute pancreatitis by inducing ferroptosis through the ACSL4/LPCAT3/ALOX15 pathway; HIF1A absence or overexpression changes SAP severity by modulating this ferroptosis pathway. Elevated lactate from glycolytic abnormalities is the upstream driver. l-Arg SAP mouse model, sh-HIF1A mice, CHIP-qPCR for HIF1A promoter lactylation, luciferase reporter, ACSL4/LPCAT3/ALOX15 expression analysis, WB for lipid peroxidation markers Journal of cellular biochemistry Medium 39676583
2023 In AML cells, EBF3 binds to the ALOX15 promoter and enhances its expression, promoting ferroptosis; this regulatory axis is confirmed by EBF3 ChIP at the ALOX15 promoter and rescue experiments with EBF3 knockdown. ChIP-qPCR of EBF3 binding at ALOX15 promoter, EBF3 overexpression/knockdown, ALOX15 ferroptosis assays in AML cells Cancer science Medium 37271497
2024 PER1 directly binds to the SREBF2 promoter to repress SREBF2 transcription; SREBF2 in turn binds to the ALOX15 promoter to repress ALOX15 transcription; PER1 overexpression thus increases ALOX15 expression and promotes ferroptosis in granulosa cells in PCOS. PER1/SREBF2 promoter binding assays (ChIP implied from 'binds to promoter'), PER1 overexpression/SREBF2 overexpression/ALOX15 silencing in granulosa cells, ferroptosis marker measurement, PCOS mouse model Biochimica et biophysica acta. Molecular basis of disease Low 38653359
2025 ALOX15 modulates ferroptosis in doxorubicin-induced cardiotoxicity via the ROS-mediated MAPK signaling pathway; ALOX15 loss of function ameliorates Dox-induced ferroptosis by inhibiting ROS-mediated MAPK activation. Linoleic acid increases susceptibility to Dox-induced damage, abolished by ALOX15 inhibition. Dox mouse and H9C2 cell models, ALOX15 inhibition/silencing/overexpression, ROS measurement, MAPK phosphorylation assays, ferroptosis markers Antioxidants & redox signaling Medium 40455659
2025 Wogonin directly binds to and inhibits ALOX15, suppressing cardiomyocyte ferroptosis in septic cardiomyopathy; pharmacological ALOX15 inhibition (ML351) recapitulates wogonin's cardioprotection. In LPS-challenged cardiomyocytes, ALOX15 overexpression or its downstream metabolite 15-HpETE abolishes the anti-ferroptotic effects of wogonin. CLP septic cardiomyopathy mouse model, molecular docking, direct binding assay, ML351 pharmacological inhibition, ALOX15 overexpression in HL-1 cardiomyocytes, 15-HpETE rescue experiment Acta pharmacologica Sinica Medium 40205009
2023 Macrophage-derived exosomal miRNA-660-5p is transported into cervical cancer cells where it attenuates ALOX15 expression to suppress ferroptosis; macrophage miRNA-660-5p upregulation depends on autocrine IL4/IL13-activated STAT6 pathway. Exosome isolation and transfer, miRNA-660-5p transfection/inhibition, ALOX15 expression analysis, ferroptosis assays in cervical cancer cells, STAT6 pathway analysis in macrophages Acta pharmaceutica Sinica. B Medium 37425043
2023 Knock-in mice expressing the arachidonic acid 15-lipoxygenating Leu353Phe Alox15 mutant (functionally humanized) develop normally and are fertile but show modified plasma oxylipidomes; aged male Alox15-KI mice develop dysfunctional erythropoiesis (reduced hematocrit, lower erythrocyte counts, attenuated hemoglobin) with improved ex vivo osmotic resistance of red blood cells, in a sex-specific manner. Alox15 Leu353Phe knock-in mouse generation, plasma oxylipidomics, hematological parameter measurement, osmotic resistance assay Cellular & molecular biology letters Medium 38030974

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2023 Alox15/15-HpETE Aggravates Myocardial Ischemia-Reperfusion Injury by Promoting Cardiomyocyte Ferroptosis. Circulation 351 36987924
2018 Emerging role of 12/15-Lipoxygenase (ALOX15) in human pathologies. Progress in lipid research 285 30472260
2022 ALOX15-launched PUFA-phospholipids peroxidation increases the susceptibility of ferroptosis in ischemia-induced myocardial damage. Signal transduction and targeted therapy 233 35970840
2004 Regulation of bone mass in mice by the lipoxygenase gene Alox15. Science (New York, N.Y.) 218 14716014
2015 Structural and functional biology of arachidonic acid 15-lipoxygenase-1 (ALOX15). Gene 178 26216303
2000 15-LOX-1: a novel molecular target of nonsteroidal anti-inflammatory drug-induced apoptosis in colorectal cancer cells. Journal of the National Cancer Institute 151 10904086
2014 Expression of inactive glutathione peroxidase 4 leads to embryonic lethality, and inactivation of the Alox15 gene does not rescue such knock-in mice. Antioxidants & redox signaling 90 25313597
2006 Reduction of isoforms of 15-lipoxygenase (15-LOX)-1 and 15-LOX-2 in human breast cancer. Prostaglandins, leukotrienes, and essential fatty acids 84 16556493
2017 Mammalian ALOX15 orthologs exhibit pronounced dual positional specificity with docosahexaenoic acid. Biochimica et biophysica acta. Molecular and cell biology of lipids 78 28400162
2020 Efferocytosis potentiates the expression of arachidonate 15-lipoxygenase (ALOX15) in alternatively activated human macrophages through LXR activation. Cell death and differentiation 70 33177619
2023 The suppression of cervical cancer ferroptosis by macrophages: The attenuation of ALOX15 in cancer cells by macrophages-derived exosomes. Acta pharmaceutica Sinica. B 67 37425043
2022 Vagus nerve stimulation promotes resolution of inflammation by a mechanism that involves Alox15 and requires the α7nAChR subunit. Proceedings of the National Academy of Sciences of the United States of America 66 35622894
2017 ALOX15 as a suppressor of inflammation and cancer: Lost in the link. Prostaglandins & other lipid mediators 66 28089732
2010 Disruption of the 12/15-lipoxygenase gene (Alox15) protects hyperlipidemic mice from nonalcoholic fatty liver disease. Hepatology (Baltimore, Md.) 62 20967760
2016 Evolutionary alteration of ALOX15 specificity optimizes the biosynthesis of antiinflammatory and proresolving lipoxins. Proceedings of the National Academy of Sciences of the United States of America 54 27412860
2023 Dihydroorotate dehydrogenase regulates ferroptosis in neurons after spinal cord injury via the P53-ALOX15 signaling pathway. CNS neuroscience & therapeutics 53 36942513
2006 The transcription factor GATA-6 is overexpressed in vivo and contributes to silencing 15-LOX-1 in vitro in human colon cancer. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 52 17167069
2022 Activation of SSAT1/ALOX15 Axis Aggravates Cerebral Ischemia/Reperfusion Injury via Triggering Neuronal Ferroptosis. Neuroscience 50 35090880
2006 Human ALOX12, but not ALOX15, is associated with BMD in white men and women. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 50 16598376
2023 Electroacupuncture Alleviates Neuropathic Pain by Suppressing Ferroptosis in Dorsal Root Ganglion via SAT1/ALOX15 Signaling. Molecular neurobiology 46 37421564
2006 Functional polymorphism in ALOX15 results in increased allele-specific transcription in macrophages through binding of the transcription factor SPI1. Human mutation 44 16320347
2024 ALOX15+ M2 macrophages contribute to epithelial remodeling in eosinophilic chronic rhinosinusitis with nasal polyps. The Journal of allergy and clinical immunology 43 38705258
2007 A near null variant of 12/15-LOX encoded by a novel SNP in ALOX15 and the risk of coronary artery disease. Atherosclerosis 43 17959182
2017 Hepatic overproduction of 13-HODE due to ALOX15 upregulation contributes to alcohol-induced liver injury in mice. Scientific reports 41 28827690
2008 Induction of arachidonate 12-lipoxygenase (Alox15) in intestine of iron-deficient rats correlates with the production of biologically active lipid mediators. American journal of physiology. Gastrointestinal and liver physiology 37 18258795
2013 Deletion of 12/15-lipoxygenase alters macrophage and islet function in NOD-Alox15(null) mice, leading to protection against type 1 diabetes development. PloS one 36 23437231
2017 Distribution of Alox15 in the Rat Brain and Its Role in Prefrontal Cortical Resolvin D1 Formation and Spatial Working Memory. Molecular neurobiology 29 28181190
2005 Association of a single nucleotide polymorphism in the lipoxygenase ALOX15 5'-flanking region (-5229G/A) with bone mineral density. Journal of bone and mineral metabolism 29 15838625
2017 Human umbilical cord mesenchymal stem cells alleviate inflammatory bowel disease through the regulation of 15-LOX-1 in macrophages. Biotechnology letters 28 28258529
2004 15-LOX-1 inhibits p21 (Cip/WAF 1) expression by enhancing MEK-ERK 1/2 signaling in colon carcinoma cells. Prostaglandins & other lipid mediators 28 15165036
2020 Tianma Gouteng granules decreases the susceptibility of Parkinson's disease by inhibiting ALOX15-mediated lipid peroxidation. Journal of ethnopharmacology 27 32259664
2019 hucMSCs Attenuate IBD through Releasing miR148b-5p to Inhibit the Expression of 15-lox-1 in Macrophages. Mediators of inflammation 27 31275059
2007 A differential association of ALOX15 polymorphisms with bone mineral density in pre- and post-menopausal women. Human heredity 27 17652958
2021 Omega-3 fatty acids protect from colitis via an Alox15-derived eicosanoid. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 26 33710695
2016 Male Subfertility Induced by Heterozygous Expression of Catalytically Inactive Glutathione Peroxidase 4 Is Rescued in Vivo by Systemic Inactivation of the Alox15 Gene. The Journal of biological chemistry 26 27634046
2013 Resolution of PMA-induced skin inflammation involves interaction of IFN-γ and ALOX15. Mediators of inflammation 26 23818745
2024 FGF21 modulates immunometabolic homeostasis via the ALOX15/15-HETE axis in early liver graft injury. Nature communications 25 39362839
2019 13-HODE, 9-HODE and ALOX15 as potential players in Rett syndrome OxInflammation. Free radical biology & medicine 25 30743046
2018 Female mice carrying a defective Alox15 gene are protected from experimental colitis via sustained maintenance of the intestinal epithelial barrier function. Biochimica et biophysica acta. Molecular and cell biology of lipids 25 29702245
2010 Selenoprotein P protects cells from lipid hydroperoxides generated by 15-LOX-1. Prostaglandins, leukotrienes, and essential fatty acids 25 20826080
2020 Suppression of Membranous LRP5 Recycling, Wnt/β-Catenin Signaling, and Colon Carcinogenesis by 15-LOX-1 Peroxidation of Linoleic Acid in PI3P. Cell reports 24 32814052
2015 Mutagenesis of triad determinants of rat Alox15 alters the specificity of fatty acid and phospholipid oxygenation. Archives of biochemistry and biophysics 24 25731857
2025 Lachnospiraceae-bacterium alleviates ischemia-reperfusion injury in steatotic donor liver by inhibiting ferroptosis via the Foxo3-Alox15 signaling pathway. Gut microbes 23 39882747
2012 Induction of apoptosis by Trichostatin A in human breast cancer cell lines: involvement of 15-Lox-1. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 23 23055198
2010 Altered epididymal sperm maturation and cytoplasmic droplet migration in subfertile male Alox15 mice. Cell and tissue research 23 20449608
2024 Alpha-tocopherol inhibits ferroptosis and promotes neural function recovery in rats with spinal cord injury via downregulating Alox15. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 22 38754264
2023 Circadian clock protein Bmal1 accelerates acute myeloid leukemia by inhibiting ferroptosis through the EBF3/ALOX15 axis. Cancer science 22 37271497
2014 15-LOX-1 suppression of hypoxia-induced metastatic phenotype and HIF-1α expression in human colon cancer cells. Cancer medicine 22 24634093
2009 15-LOX-1 transcription suppression through the NuRD complex in colon cancer cells. Oncogene 22 19198625
2009 An integrated expression phenotype mapping approach defines common variants in LEP, ALOX15 and CAPNS1 associated with induction of IL-6. Human molecular genetics 22 19942621
2024 Inhibition of SAT1 alleviates chondrocyte inflammation and ferroptosis by repressing ALOX15 expression and activating the Nrf2 pathway. Bone & joint research 21 38447596
2007 Polymorphisms in ALOX12, but not ALOX15, are significantly associated with BMD in postmenopausal women. Calcified tissue international 21 17520163
2024 Identifying ALOX15-initiated lipid peroxidation increases susceptibility to ferroptosis in asthma epithelial cells. Biochimica et biophysica acta. Molecular basis of disease 20 38641013
2023 S1PR1/S1PR3-YAP signaling and S1P-ALOX15 signaling contribute to an aggressive behavior in obesity-lymphoma. Journal of experimental & clinical cancer research : CR 20 36600310
2018 Inhibition of spinal 15-LOX-1 attenuates TLR4-dependent, nonsteroidal anti-inflammatory drug-unresponsive hyperalgesia in male rats. Pain 19 30130298
2022 The Reaction Specificity of Mammalian ALOX15 Orthologs is Changed During Late Primate Evolution and These Alterations Might Offer Evolutionary Advantages for Hominidae. Frontiers in cell and developmental biology 18 35531094
2018 Hypoxic cardiac fibroblasts from failing human hearts decrease cardiomyocyte beating frequency in an ALOX15 dependent manner. PloS one 16 30138423
2015 The role of 15-LOX-1 in colitis and colitis-associated colorectal cancer. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 16 26194111
2014 Correlation of ALOX15 expression with eosinophilic or reflux esophagitis in a cohort of pediatric patients with esophageal eosinophilia. Human pathology 16 24742828
2012 Association of ALOX15 gene polymorphism with ischemic stroke in Northern Chinese Han population. Journal of molecular neuroscience : MN 16 22351111
2008 No association of two functional polymorphisms in human ALOX15 with myocardial infarction. Atherosclerosis 16 19131063
2018 Functional characterization of novel ALOX15 orthologs representing key steps in mammalian evolution supports the Evolutionary Hypothesis of reaction specificity. Biochimica et biophysica acta. Molecular and cell biology of lipids 15 30599203
2012 Effect of genetic polymorphism of ALOX15 on aspirin-exacerbated respiratory disease. International archives of allergy and immunology 15 22652554
2024 Cerebroprotein hydrolysate-I ameliorates cognitive dysfunction in APP/PS1 mice by inhibiting ferroptosis via the p53/SAT1/ALOX15 signalling pathway. European journal of pharmacology 14 39032765
2024 Chicoric acid acts as an ALOX15 inhibitor to prevent ferroptosis in asthma. International immunopharmacology 14 39298822
2022 8-Geranyloxycarbostyril as a potent 15-LOX-1 inhibitor showed great anti-tumor effects against prostate cancer. Life sciences 14 35065164
2024 Lactate-Dependent HIF1A Transcriptional Activation Exacerbates Severe Acute Pancreatitis Through the ACSL4/LPCAT3/ALOX15 Pathway Induced Ferroptosis. Journal of cellular biochemistry 13 39676583
2023 Genipin protects against acute liver injury by abrogating ferroptosis via modification of GPX4 and ALOX15-launched lipid peroxidation in mice. Apoptosis : an international journal on programmed cell death 13 37354317
2023 Baicalein, a component of banxia xiexin decoction, alleviates CPT-11-induced gastrointestinal dysfunction by inhibiting ALOX15-mediated ferroptosis. Chemical biology & drug design 13 37735740
2015 Polymorphisms in inflammation associated genes ALOX15 and IL-6 are associated with bone properties in young women and fracture in elderly. Bone 13 26036173
2024 Mitigating phospholipid peroxidation of macrophages in stress-induced tumor microenvironment by natural ALOX15/PEBP1 complex inhibitors. Phytomedicine : international journal of phytotherapy and phytopharmacology 12 38492368
2024 Wogonin Alleviates DCD Liver Ischemia/Reperfusion Injury by Regulating ALOX15/iNOS-mediated Ferroptosis. Transplantation 12 38946036
2018 7-Farnesyloxycoumarin Exerts Anti-cancer Effects on a Prostate Cancer Cell Line by 15-LOX-1 Inhibition. Archives of Iranian medicine 12 29940744
2017 1,6-O,O-Diacetylbritannilactone Inhibits Eotaxin-1 and ALOX15 Expression Through Inactivation of STAT6 in A549 Cells. Inflammation 12 28770377
2025 ALOX15 Aggravates Metabolic Dysfunction-Associated Steatotic Liver Disease in Mice with Type 2 Diabetes via Activating the PPARγ/CD36 Axis. Antioxidants & redox signaling 11 39815992
2024 SAT1/ALOX15 Signaling Pathway Is Involved in Ferroptosis After Skeletal Muscle Contusion. International journal of molecular sciences 11 39457099
2019 15-LOX-1 has diverse roles in the resensitization of resistant cancer cell lines to doxorubicin. Journal of cellular physiology 11 31663148
2019 Deficiency of 15-LOX-1 Induces Radioresistance through Downregulation of MacroH2A2 in Colorectal Cancer. Cancers 11 31717983
2024 ALOX15-Driven Ferroptosis: The key target in Dihydrotanshinone I's epigenetic Battle in hepatic stellate cells against liver fibrosis. International immunopharmacology 10 39675198
2021 Deletion of Alox15 improves kidney dysfunction and inhibits fibrosis by increased PGD2 in the kidney. Clinical and experimental nephrology 10 33595729
2020 A role of Gln596 in fine-tuning mammalian ALOX15 specificity, protein stability and allosteric properties. Biochimica et biophysica acta. Molecular and cell biology of lipids 10 32151768
2017 ALOX15 Immunohistochemistry Aids in the Diagnosis of Eosinophilic Esophagitis on Pauci-eosinophilic Biopsies in Children. Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society 10 28812459
2017 Expression of DHA-Metabolizing Enzyme Alox15 is Regulated by Selective Histone Acetylation in Neuroblastoma Cells. Neurochemical research 10 29235036
2024 Development of novel ALOX15 inhibitors combining dual machine learning filtering and fragment substitution optimisation approaches, molecular docking and dynamic simulation methods. Journal of enzyme inhibition and medicinal chemistry 9 38213304
2022 N-Substituted 5-(1H-Indol-2-yl)-2-methoxyanilines Are Allosteric Inhibitors of the Linoleate Oxygenase Activity of Selected Mammalian ALOX15 Orthologs: Mechanism of Action. Journal of medicinal chemistry 9 35073698
2019 Association between ALOX15 gene polymorphism and brick-tea type skeletal fluorosis in Tibetans, Kazaks and Han, China. International journal of environmental health research 9 31565963
2017 Mutagenesis of Sequence Determinants of Truncated Porcine ALOX15 Induces Changes in the Reaction Specificity by Altering the Catalytic Mechanism of Initial Hydrogen Abstraction. Chemistry (Weinheim an der Bergstrasse, Germany) 9 29154477
2016 The Analgesic and Anxiolytic Effect of Souvenaid, a Novel Nutraceutical, Is Mediated by Alox15 Activity in the Prefrontal Cortex. Molecular neurobiology 9 27696115
2025 Wogonin attenuates septic cardiomyopathy by suppressing ALOX15-mediated ferroptosis. Acta pharmacologica Sinica 8 40205009
2025 ALOX15-Mediated Neuron Ferroptosis Was Involved in Diabetic Peripheral Neuropathic Pain. CNS neuroscience & therapeutics 8 40387519
2023 Silencing of ALOX15 reduces ferroptosis and inflammation induced by cerebral ischemia-reperfusion by regulating PHD2/HIF2α signaling pathway. Biotechnology & genetic engineering reviews 8 37154013
2023 Knock-in mice expressing a humanized arachidonic acid 15-lipoxygenase (Alox15) carry a partly dysfunctional erythropoietic system. Cellular & molecular biology letters 8 38030974
2022 Targeting Circulating lncRNA ENST00000538705.1 Relieves Acute Coronary Syndrome via Modulating ALOX15. Disease markers 8 35571613
2021 Conformational Heterogeneity and Cooperative Effects of Mammalian ALOX15. International journal of molecular sciences 8 33807076
2017 Effect of Alox-15 Polymorphism on GCF Levels of Lipoxin-A4 in Chronic Periodontitis: A Preliminary Study. Brazilian dental journal 8 28492741
2024 Rhythm gene PER1 mediates ferroptosis and lipid metabolism through SREBF2/ALOX15 axis in polycystic ovary syndrome. Biochimica et biophysica acta. Molecular basis of disease 7 38653359
2020 Eicosapentaenoic acid's metabolism of 15-LOX-1 promotes the expression of miR-101 thus inhibits Cox2 pathway in colon cancer. OncoTargets and therapy 7 32606775
2012 Association of ALOX15 gene polymorphisms with obesity-related phenotypes in Chinese nuclear families with male offspring. Acta pharmacologica Sinica 7 22301860
2012 Association of ALOX12 and ALOX15 gene polymorphisms with age at menarche and natural menopause in Chinese women. Menopause (New York, N.Y.) 7 22668814
2025 ALOX15 Modulates Ferroptosis via the Reactive Oxygen Species-Mediated MAPK Pathway in Doxorubicin-Induced Cardiotoxicity. Antioxidants & redox signaling 6 40455659

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