Affinage

ALOX15

Polyunsaturated fatty acid lipoxygenase ALOX15 · UniProt P16050

Length
662 aa
Mass
74.8 kDa
Annotated
2026-04-28
100 papers in source corpus 46 papers cited in narrative 46 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ALOX15 is a non-heme iron dioxygenase that oxygenates polyunsaturated fatty acids—both free and esterified in membrane phospholipids—to generate bioactive lipid mediators including 15-HpETE, 13-HODE, 12-HETE, 15-HEPE, and resolvin D1, with positional specificity (12- vs. 15-lipoxygenation) governed by conserved triad residues that evolved in higher primates to optimize 15-lipoxygenation and lipoxin synthase activity (PMID:27412860, PMID:25731857, PMID:29154477). Through these lipid products, ALOX15 drives ferroptotic cell death by peroxidizing PUFA-phosphatidylethanolamines—acting downstream of p53/SSAT1 and upstream of GPX4—and forms a complex with PEBP1 to redirect peroxidase activity toward membrane phospholipids; its metabolite 15-HpETE also promotes PGC1α ubiquitin-dependent degradation via RNF34 to attenuate mitochondrial biogenesis (PMID:35970840, PMID:36987924, PMID:35090880, PMID:38492368). ALOX15 mediates inflammation resolution by serving as the required biosynthetic enzyme for specialized proresolving mediators (SPMs) from DHA and EPA in macrophages, a function potentiated by efferocytosis-driven LXR activation and regulated by transcription factors including SPI1, MAFB, NuRD/HDAC complexes, and GATA-6 (PMID:35622894, PMID:33710695, PMID:33177619, PMID:16320347, PMID:19198625, PMID:39230290). In addition, ALOX15 suppresses Wnt/β-catenin signaling by peroxidizing PI3P to impair LRP5 endosomal recycling, regulates peak bone density as a negative regulator, is required for normal sperm cytoplasmic droplet remodeling, and contributes to hepatic lipid metabolism and neuropathic pain through cell-type-specific lipid mediator production (PMID:32814052, PMID:14716014, PMID:20449608, PMID:20967760, PMID:30130298).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 2000 High

    Establishing ALOX15 as the principal linoleic acid oxygenase in colon cells resolved the question of which enzyme generates the pro-apoptotic mediator 13-S-HODE downstream of NSAIDs, linking ALOX15 catalytic activity directly to apoptosis induction.

    Evidence Enzymatic activity assays, pharmacologic inhibition with caffeic acid, and rescue with exogenous 13-S-HODE in colorectal cancer cell lines

    PMID:10904086

    Open questions at the time
    • Upstream transcriptional mechanism by which NSAIDs induce ALOX15 was not defined
    • Whether 13-S-HODE acts through a specific receptor was not resolved
  2. 2004 High

    Demonstration that Alox15 knockout improves bone mineral density in mice established ALOX15 as a negative regulator of bone formation, revealing an unexpected physiological role beyond classical eicosanoid biology.

    Evidence Alox15 KO mouse crosses and pharmacologic inhibitor treatment with bone density and strength measurements

    PMID:14716014

    Open questions at the time
    • The specific lipid mediator and downstream pathway by which ALOX15 suppresses osteoblast activity was not identified
    • Human genetic validation was lacking
  3. 2006 High

    Identification of SPI1 binding to a promoter polymorphism and NuRD/HDAC-mediated repression at the ALOX15 promoter established the first transcriptional regulatory mechanisms controlling cell-type-specific ALOX15 expression.

    Evidence EMSA, reporter assays with mutagenesis in macrophages (SPI1); ChIP, siRNA knockdown, and HDAC inhibitor treatment in colon cancer cells (NuRD)

    PMID:16320347 PMID:17167069 PMID:19198625

    Open questions at the time
    • How SPI1 and NuRD regulatory circuits integrate in immune cells was not addressed
    • GATA-6 contribution required combination treatment, suggesting it is a co-factor rather than primary regulator
  4. 2007 High

    Characterization of the T560M near-null coding variant provided the first human genetic evidence that ALOX15 catalytic activity varies substantially in the population, with implications for disease susceptibility studies.

    Evidence Resequencing and in vitro catalytic activity assay of T560M vs. wild-type ALOX15

    PMID:17959182

    Open questions at the time
    • Population frequency and clinical phenotypic consequences of T560M were not established
    • No structural explanation for the ~20-fold activity reduction was provided
  5. 2010 High

    Discovery that Alox15 is required for sperm cytoplasmic droplet remodeling and organelle clearance during epididymal maturation revealed a specialized developmental function in male germ cells, later confirmed by genetic epistasis with Gpx4.

    Evidence Alox15-KO sperm ultrastructural analysis by TEM; genetic epistasis with Gpx4 Sec46Ala heterozygotes restoring sperm motility and fertility

    PMID:20449608 PMID:27634046

    Open questions at the time
    • The specific ALOX15-derived lipid mediator driving organelle clearance in sperm was not identified
    • Whether this function is conserved in human spermatogenesis is unknown
  6. 2010 High

    Double-KO studies showed Alox15 disruption protects against hepatic steatosis and insulin resistance in hyperlipidemic mice, establishing ALOX15 as a driver of hepatic lipid pathology through JNK/AMPK and IRS-2 modulation.

    Evidence ApoE−/−/Alox15−/− double-knockout mouse, phosphorylation assays, hepatocyte apoptosis assay

    PMID:20967760

    Open questions at the time
    • The direct ALOX15 lipid mediator responsible for hepatic signaling was not fully defined
    • Applicability to non-hyperlipidemic hepatic disease was untested
  7. 2014 High

    Genetic epistasis showed that Alox15 deletion does not rescue Gpx4 catalytic-null embryonic lethality, establishing that ALOX15 is not the sole oxidative driver of Gpx4-dependent developmental lethality despite its role in ferroptosis.

    Evidence Crossbreeding of Gpx4 Sec46Ala knock-in with Alox15-KO mice, embryonic viability assessment

    PMID:25313597

    Open questions at the time
    • Which other lipoxygenases or non-enzymatic pathways compensate in the Gpx4-null embryonic context was not determined
  8. 2015 High

    Systematic mutagenesis of triad determinants (Leu353, Ile593) and Val418/Val419 across species orthologs, combined with QM/MM calculations, resolved the structural basis of 12- vs. 15-lipoxygenation specificity and demonstrated that ALOX15 evolved 15-lipoxygenating capability in higher primates to optimize lipoxin synthase activity.

    Evidence Recombinant mutagenesis, in vitro enzymatic assays across multiple orthologs, QM/MM calculations of hydrogen abstraction energy barriers

    PMID:25731857 PMID:27412860 PMID:28400162 PMID:29154477

    Open questions at the time
    • Crystal structures of substrate-bound human ALOX15 confirming the QM/MM predictions are lacking
    • How positional specificity changes affect in vivo SPM profiles in primates was not tested
  9. 2017 High

    Localization and functional studies in prefrontal cortex established that ALOX15 converts DHA to 17S-HDHA/resolvin D1 in neurons, directly linking ALOX15 to synaptic plasticity (LTP) and spatial working memory.

    Evidence RT-PCR, immuno-EM localization, LC-MS quantification, in vivo Alox15 inhibition/antisense knockdown with T-maze and LTP electrophysiology

    PMID:28181190

    Open questions at the time
    • The receptor through which resolvin D1 modulates LTP was not identified
    • Whether neuronal ALOX15 is relevant to human cognitive function is untested
  10. 2018 High

    Demonstration that spinal microglial ALOX15 mediates TLR4-dependent hepoxilin production and tactile allodynia identified a cell-type-specific pro-nociceptive role, with selective ALOX15 inhibitors (ML127, ML351) fully abrogating pain behavior.

    Evidence Primary spinal microglia culture, HEK-293T heterologous expression with selective inhibitors, intrathecal TLR4 activation model

    PMID:30130298

    Open questions at the time
    • Whether ALOX15-dependent allodynia operates in chronic pain conditions beyond TLR4 activation was not explored
    • The hepoxilin receptor mediating nociception was not identified
  11. 2018 High

    Characterization of ALOX15 products (12S-HETE) compromising tight junction integrity (ZO-1) in colon epithelium, combined with KO protection from colitis, established a mechanism by which ALOX15 promotes intestinal barrier dysfunction.

    Evidence Alox15-KO and human ALOX15 transgenic mice in DSS colitis model, transepithelial resistance assay with enantioselective 12S-HETE

    PMID:29702245

    Open questions at the time
    • The receptor or signaling pathway through which 12S-HETE reduces ZO-1 was not defined
    • Whether the protective vs. pro-resolving roles of ALOX15 in colitis are sex-dependent was not fully explored
  12. 2020 High

    Discovery that ALOX15 peroxidizes PI3P to generate PI3P-13-HODE, which disrupts SNX17-LRP5 binding, inhibits LRP5 recycling, and suppresses Wnt/β-catenin signaling, revealed a novel non-classical mechanism linking lipid peroxidation to endosomal sorting and tumor suppression.

    Evidence ALOX15 transgenic mouse intestine, APC-mutant model, PI3P-lipid binding assays, endosome tracking

    PMID:32814052

    Open questions at the time
    • Whether PI3P peroxidation affects other PI3P-dependent endosomal cargo is unknown
    • Structural basis for loss of SNX17 binding to oxidized PI3P was not determined
  13. 2020 High

    Efferocytosis was shown to potentiate ALOX15 expression in human macrophages through LXR activation, linking phagocytic clearance of apoptotic cells to amplified SPM biosynthesis and establishing a feedforward resolution circuit.

    Evidence Primary human macrophage efferocytosis assay, LXR agonist and NPC1 inhibition, LXRα/β siRNA, LC-MS/MS lipid mediator profiling

    PMID:33177619

    Open questions at the time
    • Whether LXR directly binds the ALOX15 promoter or acts indirectly was not resolved
    • The contribution of other LXR target genes to SPM amplification was not isolated
  14. 2021 High

    Genetic epistasis confirmed that the anti-colitis effect of elevated tissue n-3 PUFAs requires Alox15, with 15S-HEPE identified as a sufficient protective mediator, resolving the question of which enzyme converts dietary omega-3 fatty acids into bioactive anti-inflammatory products in vivo.

    Evidence Fat1 transgenic × Alox15-KO crossbreeding, DSS/TNBS colitis models, lipid mediator analysis, 15-HEPE rescue

    PMID:33710695

    Open questions at the time
    • The receptor and signaling pathway through which 15S-HEPE protects from colitis was not identified
  15. 2022 High

    Multi-omics and chemogenetic studies established ALOX15 as the primary initiator of PUFA-phospholipid peroxidation (specifically PE-PUFAs) in cardiomyocytes during ischemia-reperfusion, positioning it as a 'burning point' for ferroptotic signaling.

    Evidence Multi-omics with chemogenetic approaches in animal and cellular models of cardiac I/R

    PMID:35970840

    Open questions at the time
    • How ALOX15 is activated or stabilized specifically during ischemia-reperfusion was not mechanistically defined
  16. 2022 High

    ALOX15 was placed as a required mediator of vagus nerve stimulation-driven SPM biosynthesis, establishing the neuro-immune mechanism by which cholinergic anti-inflammatory signaling resolves inflammation through ALOX15-dependent lipid mediator production.

    Evidence Electrical VNS in Alox15-KO mice, lipid mediator metabololipidomics in zymosan peritonitis model

    PMID:35622894

    Open questions at the time
    • The cell type mediating VNS-dependent ALOX15 activation was not identified
    • Whether VNS directly upregulates ALOX15 or increases substrate availability was not resolved
  17. 2023 High

    Identification that 15-HpETE promotes PGC1α binding to the E3 ligase RNF34, leading to PGC1α ubiquitin-dependent degradation and attenuated mitochondrial biogenesis, revealed a mechanistic link between ALOX15 catalytic products and mitochondrial dysfunction in ferroptotic cardiomyocytes.

    Evidence Myocardial-specific ALOX15 KO mice, co-IP of PGC1α-RNF34, metabolomics, pharmacologic inhibition with ML351

    PMID:36987924

    Open questions at the time
    • Whether 15-HpETE acts directly on PGC1α or RNF34 to promote their interaction is not structurally resolved
    • Generalizability of this mechanism to non-cardiac ferroptosis contexts is untested
  18. 2024 Medium

    MAFB was identified as a direct transcriptional regulator of ALOX15 in macrophages during ischemic AKI, operating downstream of the COX-2/PGE2/EP4 pathway to mediate a lipid mediator class switch from pro-inflammatory to proresolving, answering how macrophage phenotype transitions engage ALOX15 transcription.

    Evidence Macrophage-specific Mafb-KO mice, AKI model, in vitro PGE2/EP4 pathway assay, lipid mediator profiling

    PMID:39230290

    Open questions at the time
    • Whether MAFB binds the ALOX15 promoter directly was not confirmed by ChIP
    • Generalizability beyond renal I/R macrophages is unknown
  19. 2024 Medium

    Co-immunoprecipitation and microscale thermophoresis confirmed that ALOX15 forms a functional complex with PEBP1 in macrophages, redirecting its peroxidase activity toward membrane phospholipids; disruption of this complex inhibits phospholipid peroxidation and ferroptosis.

    Evidence Co-IP, MST biophysical binding, LC-MS/MS phospholipidomics, molecular docking, in vivo and in vitro functional verification

    PMID:38492368

    Open questions at the time
    • Structural basis of the ALOX15-PEBP1 interface in the context of membrane substrates is not resolved
    • Independent replication in a second laboratory is needed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the crystal structure of substrate-bound human ALOX15, the identity of receptors for many ALOX15-derived lipid mediators (hepoxilins, 15-HEPE, 13-S-HODE), the mechanism by which ALOX15 is selectively activated during ischemia, and how the pro-inflammatory versus pro-resolving functions of ALOX15 are spatiotemporally segregated within the same cell type.
  • No substrate-bound crystal structure of human ALOX15 exists
  • Receptors for many ALOX15 products remain unidentified
  • Spatiotemporal regulation of pro- vs. anti-inflammatory ALOX15 activity in single cells is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 6 GO:0008289 lipid binding 3
Localization
GO:0005829 cytosol 2 GO:0005886 plasma membrane 2 GO:0005768 endosome 1
Pathway
R-HSA-1430728 Metabolism 6 R-HSA-5357801 Programmed Cell Death 6 R-HSA-168256 Immune System 5 R-HSA-162582 Signal Transduction 2
Partners
GPX4HDAC1LRP5MAFBMTA1PEBP1RNF34SPI1
Complex memberships
ALOX15-PEBP1 complex

Evidence

Reading pass · 46 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2023 ALOX15 metabolite 15-HpETE promotes binding of PGC1α to the ubiquitin ligase RNF34, leading to ubiquitin-dependent degradation of PGC1α, attenuated mitochondrial biogenesis, and cardiomyocyte ferroptosis during myocardial ischemia-reperfusion injury. Loss/gain-of-function mouse models, metabolomics, co-immunoprecipitation, myocardial-specific knockout, pharmacologic inhibition (ML351) Circulation High 36987924
2022 ALOX15 is the primary mediator of ischemia-provoked PUFA-phospholipid peroxidation (specifically oxidized PUFAs in phosphatidylethanolamines) in cardiomyocytes, acting as a 'burning point' that initiates ferroptotic signals during reperfusion. Multi-omics, chemogenetic approaches, animal and in vitro models Signal transduction and targeted therapy High 35970840
2000 15-LOX-1 (ALOX15) is the main enzyme for metabolizing linoleic acid to 13-S-HODE in colon cells; NSAIDs increase 15-LOX-1 protein expression and enzymatic activity, and 13-S-HODE is the proximate inducer of apoptosis — inhibiting 15-LOX-1 blocks NSAID-induced apoptosis, which is restored by exogenous 13-S-HODE. Enzymatic activity assay, protein expression (Western blot), pharmacologic inhibition (caffeic acid), rescue with exogenous 13-S-HODE in colorectal cancer cell lines Journal of the National Cancer Institute High 10904086
2004 Alox15 (12/15-lipoxygenase) acts as a negative regulator of peak bone mineral density in mice; pharmacologic inhibitors of Alox15 improve bone density and strength in rodent osteoporosis models. Genetic crossbreeding with Alox15 knockout mice, pharmacologic inhibition, bone density/strength measurement Science High 14716014
2016 The reaction specificity of mammalian ALOX15 evolved during late primate evolution: lower primates express 12-lipoxygenating ALOX15 orthologs, while higher primates (including humans) express 15-lipoxygenating enzymes; this switch optimizes lipoxin synthase activity, with 15-lipoxygenating variants having >5-fold higher lipoxin synthase activity. QM/MM calculations show lower energy barriers for C13-hydrogen abstraction (15-lipoxygenation) in rabbit ALOX15. Cloning and functional characterization of multiple ALOX15 orthologs, in vitro enzymatic assays, site-directed mutagenesis, molecular dynamics simulations, QM/MM calculations Proceedings of the National Academy of Sciences High 27412860
2015 Mutagenesis of triad determinants (Leu353, Ile593) in rat Alox15 alters positional specificity for both free fatty acids and complex ester lipids; rat Alox15 and its 15-lipoxygenating Leu353Phe mutant can oxygenate ester lipids of biomembranes and HDL. Recombinant protein expression, multiple directed mutagenesis, in vitro enzymatic assays with free and esterified substrates Archives of biochemistry and biophysics High 25731857
2017 Human ALOX15, chimpanzee, and orangutan orthologs exhibit pronounced dual positional specificity with DHA, forming similar amounts of 14- and 17-HpDHA; ALOX15 orthologs preferentially oxygenate DHA and EPA over arachidonic acid when supplied simultaneously. Recombinant expression of ALOX15 orthologs from eight mammalian species, in vitro enzymatic assays with multiple PUFA substrates Biochimica et biophysica acta. Molecular and cell biology of lipids High 28400162
2020 15-LOX-1 peroxidation of linoleic acid in phosphatidylinositol-3-phosphates (PI3P_LA) generates PI3P_13-HODE, which decreases PI3P binding to SNX17 and LRP5, inhibits LRP5 recycling from endosomes to the plasma membrane, increases LRP5 lysosomal degradation, and suppresses Wnt/β-catenin signaling to inhibit colorectal carcinogenesis. 15-LOX-1 transgenic mouse intestinal expression, APC-mutant mouse model, in vitro mechanistic studies with PI3P-lipid binding assays, endosome tracking Cell reports High 32814052
2006 A C-to-T polymorphism at position c.-292 in the ALOX15 promoter creates a novel binding site for the transcription factor SPI1 (PU.1), resulting in ~3-fold higher ALOX15 transcription in macrophages that constitutively express SPI1; mutation of the SPI1 core binding site abolishes higher transcriptional activity. Promoter transcription assays, electrophoretic mobility shift assay (EMSA), site-directed mutagenesis, primary human macrophage mRNA quantification Human mutation High 16320347
2009 15-LOX-1 transcription is repressed in colon cancer cells through recruitment of the NuRD repressor complex (containing MTA1 and HDAC1) to the -120 to -391 region of the 15-LOX-1 promoter; HDAC inhibitors reduce NuRD recruitment and activate 15-LOX-1 transcription, while siRNA knockdown of MTA1 or HDAC1 activates 15-LOX-1. Chromatin immunoprecipitation, siRNA knockdown, luciferase reporter assays, HDAC inhibitor treatment Oncogene High 19198625
2006 GATA-6 overexpression contributes to transcriptional silencing of 15-LOX-1 in colon cancer cells; GATA-6 siRNA knockdown contributes to restoring 15-LOX-1 expression and inducing apoptosis when combined with NSAID or HDAC inhibitor treatment. GATA-6 siRNA transfection, gene expression analysis, cell proliferation and apoptosis assays in colon cancer cells FASEB journal Medium 17167069
2014 Homozygous Alox15 deficiency does not rescue embryonic lethality of mice expressing catalytically inactive Gpx4 (Sec46Ala), indicating that Alox15 pro-oxidative activity is not the primary driver of lethality caused by loss of Gpx4 catalytic function. Genetic epistasis via crossbreeding Gpx4 knock-in and Alox15 knockout mice, embryonic viability assessment Antioxidants & redox signaling High 25313597
2016 Systemic inactivation of the Alox15 gene in male mice heterozygous for catalytically inactive Gpx4 (Sec46Ala) normalizes sperm motility, midpiece structure, and fertility, demonstrating that ALOX15 pro-oxidative activity directly counteracts Gpx4-dependent antioxidant protection in sperm. Genetic epistasis: crossbreeding Sec46Ala-Gpx4+/- mice with Alox15-/- mice, sperm motility analysis, fertility assessment, structural EM The Journal of biological chemistry High 27634046
2010 Alox15 (15-lipoxygenase) in sperm cytoplasmic droplets is required for normal epididymal sperm maturation and cytoplasmic droplet migration; Alox15-null males retain cytoplasmic droplets with intact mitochondria, unlike wild-type where droplets contain only hollow membrane vesicles. Differential interference contrast microscopy, transmission electron microscopy of Alox15-knockout vs. wild-type sperm Cell and tissue research High 20449608
2010 ALOX15 disruption in hyperlipidemic ApoE-/- mice reduces hepatic steatosis, inflammation, and insulin resistance; absence of Alox15 upregulates insulin receptor substrate-2, exerts opposing effects on JNK and AMPK phosphorylation, and protects hepatocytes from TNFα-induced apoptosis. Double-knockout mouse model (ApoE-/-/Alox15-/-), gene expression, phosphorylation assays, isolated hepatocyte apoptosis assay Hepatology High 20967760
2022 Vagus nerve stimulation (VNS) promotes resolution of inflammation in zymosan-induced peritonitis by increasing specialized proresolving mediators (SPMs) from the DHA and DPA metabolomes; this effect is abolished in Alox15-deficient mice, placing Alox15 as a required mediator of VNS-driven SPM biosynthesis. Electrical VNS in Alox15-knockout mice, lipid mediator metabololipidomics, peritonitis model Proceedings of the National Academy of Sciences High 35622894
2021 The anti-colitis protective effect of elevated n-3 PUFA tissue status in fat1 transgenic mice requires Alox15; Alox15 deficiency counteracts protection by suppressing 15-HEPE formation, and intraperitoneal 15S-HEPE treatment alone protects wild-type mice from colitis. Fat1 transgenic × Alox15-/- crossbreeding, DSS and TNBS colitis models, lipid mediator analysis, 15-HEPE administration FASEB journal High 33710695
2018 Female Alox15-/- mice are protected from DSS-induced colitis; mechanistically, the major Alox15 product in mice (12S-HETE) enantioselectively compromises transepithelial electric resistance and reduces ZO-1 tight junction protein expression in colon epithelial cells, while human ALOX15 transgenic overexpression intensifies colitis. Alox15 KO mice, DSS colitis model, in vitro transepithelial resistance assay with exogenous 12S-HETE, ZO-1 expression analysis, transgenic overexpression Biochimica et biophysica acta. Molecular and cell biology of lipids High 29702245
2013 12/15-LO (Alox15) is expressed in macrophages but not B or T cells in NOD mice; Alox15 deletion reduces proinflammatory cytokine expression in macrophages and prevents diabetes transfer by splenocytes, while also maintaining islet transcription factor expression and beta cell mass. qRT-PCR of immune cell subsets, NOD-Alox15null mouse, adoptive transfer assay, beta cell mass measurement PloS one High 23437231
2017 ALOX15 upregulation in the liver produces 13-HODE from linoleic acid, which induces oxidative stress, ER stress, and apoptosis in hepatocytes; ALOX15 knockout prevents alcohol-induced liver damage, and linoleic acid (not ethanol or acetaldehyde) induces ALOX15 expression in hepatocytes. ALOX15 knockout mice, pharmacologic inhibitor (PD146176), hepatocyte culture with 13-HODE, ALOX15 induction assay Scientific reports High 28827690
2020 Efferocytosis potentiates ALOX15 expression in alternatively activated human macrophages via LXR activation: AC uptake upregulates LXR-dependent gene expression (suppressed by NPC1 inhibition), and LXR/IL-13 co-stimulation enhances ALOX15 expression and increases SPM precursor (15-HETE, 17-HDHA, resolvin D5) synthesis; LXRα/β silencing attenuates this potentiation. Primary human macrophage efferocytosis assay, LXR agonist treatment, NPC1 inhibition, LXRα/β siRNA silencing, global transcriptome analysis, LC-MS/MS lipid mediator quantification Cell death and differentiation High 33177619
2007 A coding SNP in ALOX15 (T560M) results in a ~20-fold reduction in catalytic activity in vitro, creating a near-null variant of human 12/15-LOX. ALOX15 resequencing, in vitro catalytic activity assay of 560M vs. 560T variants Atherosclerosis High 17959182
2017 Alox15 in the prefrontal cortex metabolizes DHA to 17S-hydroxy-DHA, which is converted to resolvin D1; inhibition or antisense knockdown of Alox15 in the prefrontal cortex reduces resolvin D1 levels, blocks hippocampo-prefrontal cortical LTP, and impairs spatial working memory. RT-PCR, Western blot, immunohistochemistry, immuno-electron microscopy, LC-MS quantification, Alox15 inhibition/antisense knockdown in vivo, T-maze and LTP assays Molecular neurobiology High 28181190
2018 Hypoxic cardiac fibroblasts from failing hearts increase ALOX15 expression and produce 15-HETE; conditioned medium from these fibroblasts decreases beating frequency of human iPSC-derived cardiomyocytes in an ALOX15-dependent manner. Cardiac fibroblast isolation, hypoxic culture, gene expression, 15-HETE measurement, conditioned medium transfer to iPS-cardiomyocytes, calcium imaging PloS one Medium 30138423
2017 Alox15 expression in mouse prefrontal cortex is regulated epigenetically by histone acetylation; HDAC inhibitors (trichostatin A, sodium butyrate) and class I-specific HDAC inhibitors upregulate Alox15, while the p300 HAT inhibitor C646 modulates this upregulation, implicating p300 HAT in differentiation-associated Alox15 upregulation in neurons. HDAC inhibitor treatment of SH-SY5Y cells, p300 HAT inhibitor co-treatment, retinoic acid differentiation, mRNA expression analysis, primary cortical neuron development time-course Neurochemical research Medium 29235036
2004 15-LOX-1 overexpression in HCT-116 colon cancer cells induces ERK1/2 phosphorylation, decreases p21(Cip/WAF1) expression, and increases cell growth; the LOX inhibitor NDGA reverses these effects, identifying 13-S-HODE as the active metabolite mediating MEK-ERK1/2 signaling. 15-LOX-1 transfection, ERK1/2 phosphorylation assay, p21 expression analysis, LOX inhibitor (NDGA) treatment, sodium butyrate/13-S-HODE treatment Prostaglandins & other lipid mediators Medium 15165036
2010 Selenoprotein P (SelP) exhibits in vitro lipid hydroperoxidase activity against 15-HpETE produced by ALOX15, attenuating 15-HpETE oxidation in cellular assays and in a transcellular model where ALOX15 is metabolically active, establishing SelP as an extracellular antioxidant defense against ALOX15 products. In vitro hydroperoxidase assay, cellular 15-HpETE oxidation assay, transcellular assay with metabolically active 15-LOX-1 Prostaglandins, leukotrienes, and essential fatty acids Medium 20826080
2022 SSAT1 activation upregulates ALOX15 expression in primary cortical neurons; SSAT1 knockdown downregulates ALOX15 and reduces ferroptosis (lipid hydroperoxide production, viability loss) in neurons treated with oxidative stress; SSAT1 overexpression decreases GPX4 and SLC7A11 expression; ALOX15 inhibitor PD146176 partially reverses SSAT1-induced ferroptosis, placing ALOX15 downstream of SSAT1 in neuronal ferroptosis. SSAT1 siRNA/overexpression in primary neurons, ALOX15 inhibitor treatment, viability assay, lipid hydroperoxide measurement, GPX4/SLC7A11 expression analysis, rat I/R model Neuroscience Medium 35090880
2023 DHODH inhibits the P53/ALOX15 signaling pathway in neurons to reduce ferroptosis after spinal cord injury; DHODH decreases P53 expression, which in turn suppresses ALOX15 expression and reduces lipid peroxide production and mitochondrial damage. Rat SCI model, erastin-induced PC12 cells, molecular and histological ferroptosis assessment, DHODH modulation, P53/ALOX15 pathway analysis CNS neuroscience & therapeutics Medium 36942513
2024 FGF21 deficiency leads to abnormal activation of the ALOX15/15-HETE pathway, triggering innate immunity-dominated pro-inflammatory responses in liver grafts during ischemia/reperfusion injury; pharmacological FGF21 administration suppresses this pathway and protects against hepatic I/R injury. Male mouse models of hepatic I/R injury and orthotopic LT, FGF21-deficient mice, arachidonic acid metabolomics, pharmacologic FGF21 administration Nature communications Medium 39362839
2024 MAFB transcription factor in macrophages directly regulates ALOX15 expression during ischemic acute kidney injury; macrophage-specific Mafb deficiency significantly decreases Alox15 mRNA and protein in infiltrating macrophages; in vitro, MAFB regulates Alox15 expression under the COX-2/PGE2/EP4 pathway, mediating a lipid mediator class switch from pro-inflammatory to proresolving mediators. Macrophage-specific Mafb-KO mice, ischemia-reperfusion AKI model, mRNA/protein analysis, in vitro PGE2/EP4 pathway assay, lipid mediator profiling Journal of immunology Medium 39230290
2024 ALOX15 forms a complex with PEBP1 (phosphatidylethanolamine-binding protein 1) in macrophages under psychological stress, mediating membrane phospholipid peroxidation; disruption of this ALOX15/PEBP1 interaction (by DZXY components) inhibits phospholipid peroxidation and restores macrophage phagocytic capacity. Confirmed by co-immunoprecipitation and microscale thermophoresis. LC-MS/MS phospholipidomics, co-immunoprecipitation, microscale thermophoresis (MST), molecular docking, activity verification, flow cytometry Phytomedicine Medium 38492368
2021 Conformational heterogeneity of rabbit ALOX15 and human ALOX15B: native PAGE shows two conformers with distinct electrophoretic mobilities; MD simulations indicate substrate-bound geometry at the active site affects dimer interface geometry; Gln596 mutations impair allosteric properties as shown by kinetics and MD. Native PAGE, site-directed mutagenesis, MD simulations, in silico docking, kinetic measurements International journal of molecular sciences Medium 33807076
2020 Gln596 in mammalian ALOX15 does not directly interact with the carboxylate of arachidonic acid; instead, mutations at Gln596 destabilize ALOX15 secondary and tertiary structure by disrupting local electrostatic interactions, and impair allosteric properties by altering dimer interface geometry. Site-directed mutagenesis, in silico substrate docking, molecular dynamics simulations, enzyme kinetics, structural assays of rabbit and human ALOX15 Biochimica et biophysica acta. Molecular and cell biology of lipids Medium 32151768
2022 N-substituted 5-(1H-indol-2-yl)-2-methoxyaniline derivatives are allosteric inhibitors that selectively inhibit the linoleate oxygenase activity of rabbit and human ALOX15 without affecting arachidonic acid oxygenation; MD simulations using a dimer model suggest inhibitor binding at one monomer active site induces conformational changes in the other monomer impairing productive linoleic acid complex formation. Synthesis of inhibitor series, steady-state enzyme kinetics, mutagenesis studies, molecular dynamics simulations of ALOX15 dimer Journal of medicinal chemistry Medium 35073698
2017 Mutagenesis of Val418 and Val419 sequence determinants in porcine ALOX15 (arachidonic acid 12-lipoxygenating) converts it to a dominantly 15-lipoxygenating enzyme; QM/MM calculations show that the Val418Ile+Val419Met double mutant lowers the energy barrier for 15-lipoxygenation relative to 12-lipoxygenation, altering the catalytic mechanism of initial hydrogen abstraction. Site-directed mutagenesis, docking and MD simulations, QM/MM calculations, in vitro enzymatic assay Chemistry (Weinheim) High 29154477
2008 Induction of Alox15 in the intestine of iron-deficient rats leads to production of biologically active lipid molecules (12-HETE, 13-HODE, 13-HOTE) as shown by HPLC analysis, perturbing intestinal lipid homeostasis. Gene chip studies, TaqMan RT-PCR, polyclonal antibody protein detection, HPLC lipid analysis in iron-deficient rats and Belgrade rats American journal of physiology. Gastrointestinal and liver physiology Medium 18258795
2011 ALOX15 expression in colon cancer cells suppresses HIF-1α protein expression and stability under hypoxia, inhibiting VEGF expression, angiogenesis, and cancer cell migration and invasion. 15-LOX-1 reexpression in multiple colon cancer cell lines (HCT116, HT29LMM, LoVo), HIF-1α stability assay, VEGF measurement, migration/invasion assay, angiogenesis assay Cancer medicine Medium 24634093
2023 Macrophage-derived exosomes containing miRNA-660-5p are transported into cervical cancer cells where miRNA-660-5p attenuates ALOX15 expression to suppress ferroptosis; upregulation of miRNA-660-5p in macrophages is driven by autocrine IL-4/IL-13-activated STAT6 pathway. Exosome isolation and transfer, miRNA-660-5p overexpression/knockdown, ALOX15 expression analysis, ferroptosis assays, STAT6 pathway inhibition, in vivo tumor models Acta pharmaceutica Sinica B Medium 37425043
2025 ALOX15 aggravates MASLD/steatotic liver disease via the PPARγ/CD36 axis: ALOX15 overexpression increases fatty acid uptake and triglyceride accumulation; PPARγ antagonist GW9662 or CD36 inhibitor blocks ALOX15-mediated lipid accumulation; liraglutide (GLP-1RA) improves hepatic lipid accumulation by suppressing the ALOX15/PPARγ/CD36 pathway. ALOX15 lentiviral overexpression and siRNA knockdown in HepG2 cells, transcriptomics, metabolomics, pharmacologic inhibition of PPARγ/CD36, HFD/STZ mouse model Antioxidants & redox signaling Medium 39815992
2023 Bmal1 in AML cells recruits EZH2 to the EBF3 promoter, enhancing its methylation and suppressing EBF3 expression; EBF3 binds the ALOX15 promoter to enhance ALOX15 expression, promoting ferroptosis; Bmal1 therefore suppresses ALOX15-mediated ferroptosis via EZH2/EBF3 axis. ChIP for EZH2 at EBF3 promoter, EBF3 ChIP at ALOX15 promoter, Bmal1 overexpression/knockdown, EBF3 knockdown, ferroptosis assays, xenograft model Cancer science Medium 37271497
2024 PER1 binds the SREBF2 promoter to repress SREBF2 transcription; SREBF2 in turn binds the ALOX15 promoter to repress ALOX15 transcription; thus PER1 promotes ALOX15-mediated ferroptosis in granulosa cells in PCOS by removing SREBF2-mediated repression of ALOX15. ChIP-qPCR, promoter binding assays, PER1 overexpression, SREBF2 overexpression/knockdown, ALOX15 silencing, ferroptosis assays in granulosa cells Biochimica et biophysica acta. Molecular basis of disease Medium 38653359
2024 DHI (dihydrotanshinone I) upregulates EGR1, leading to decreased DNMT1 expression, increased ALOX15 demethylation, and ALOX15-dependent ferroptosis induction in hepatic stellate cells; EGR1 is a direct pharmacological target of DHI confirmed by molecular docking. Transcriptome sequencing, qRT-PCR, Western blot, DNMT1 overexpression, ALOX15 siRNA, methylation analysis, molecular docking International immunopharmacology Medium 39675198
2024 Lachnospiraceae-derived pyruvate inhibits ALOX15 expression and reduces ferroptosis in donor livers during transplantation I/R injury; reduced nuclear translocation of Foxo3 further suppresses ALOX15 expression, identifying a Foxo3-Alox15 axis. Multi-omics, Lachnospiraceae treatment in rat LT models, Foxo3 nuclear translocation analysis, Alox15 expression measurement, ferroptosis assays Gut microbes Medium 39882747
2018 Spinal microglial ALOX15 (15-LOX-1) mediates TLR4-dependent hepoxilin production and tactile allodynia; intrathecal TLR4 activation increases 15-LOX-1 expression in primary spinal microglia (but not astrocytes) and hepoxilin production; selective 15-LOX-1 inhibitors (ML127, ML351) reduce activity of rat 15-LOX-1 expressed in HEK-293T cells and completely abrogate TLR4-induced allodynia. Intrathecal KLA administration, primary spinal microglia/astrocyte culture, selective antibody targeting, HEK-293T heterologous expression with inhibitor assay, in vivo pharmacology Pain High 30130298
2024 HIF1A, whose transcription is enhanced by lactate-driven histone lactylation at its promoter, activates the ACSL4/LPCAT3/ALOX15 pathway to induce ferroptosis in severe acute pancreatitis; sh-HIF1A reduces ALOX15 expression and ferroptosis markers; ChIP-qPCR confirms HIF1A promoter binding. sh-HIF1A mice, SAP mouse model, ChIP-qPCR, luciferase reporter, Western blot, qPCR, ferroptosis marker measurement Journal of cellular biochemistry Medium 39676583

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 324 36987924
2018 Emerging role of 12/15-Lipoxygenase (ALOX15) in human pathologies. Progress in lipid research 280 30472260
2022 ALOX15-launched PUFA-phospholipids peroxidation increases the susceptibility of ferroptosis in ischemia-induced myocardial damage. Signal transduction and targeted therapy 219 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 173 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 150 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 88 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 83 16556493
2017 Mammalian ALOX15 orthologs exhibit pronounced dual positional specificity with docosahexaenoic acid. Biochimica et biophysica acta. Molecular and cell biology of lipids 76 28400162
2020 Efferocytosis potentiates the expression of arachidonate 15-lipoxygenase (ALOX15) in alternatively activated human macrophages through LXR activation. Cell death and differentiation 68 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 65 37425043
2017 ALOX15 as a suppressor of inflammation and cancer: Lost in the link. Prostaglandins & other lipid mediators 65 28089732
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 63 35622894
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 53 27412860
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
2023 Dihydroorotate dehydrogenase regulates ferroptosis in neurons after spinal cord injury via the P53-ALOX15 signaling pathway. CNS neuroscience & therapeutics 51 36942513
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
2022 Activation of SSAT1/ALOX15 Axis Aggravates Cerebral Ischemia/Reperfusion Injury via Triggering Neuronal Ferroptosis. Neuroscience 48 35090880
2006 Functional polymorphism in ALOX15 results in increased allele-specific transcription in macrophages through binding of the transcription factor SPI1. Human mutation 44 16320347
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
2023 Electroacupuncture Alleviates Neuropathic Pain by Suppressing Ferroptosis in Dorsal Root Ganglion via SAT1/ALOX15 Signaling. Molecular neurobiology 42 37421564
2017 Hepatic overproduction of 13-HODE due to ALOX15 upregulation contributes to alcohol-induced liver injury in mice. Scientific reports 41 28827690
2024 ALOX15+ M2 macrophages contribute to epithelial remodeling in eosinophilic chronic rhinosinusitis with nasal polyps. The Journal of allergy and clinical immunology 40 38705258
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
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 Distribution of Alox15 in the Rat Brain and Its Role in Prefrontal Cortical Resolvin D1 Formation and Spatial Working Memory. Molecular neurobiology 28 28181190
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
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
2020 Tianma Gouteng granules decreases the susceptibility of Parkinson's disease by inhibiting ALOX15-mediated lipid peroxidation. Journal of ethnopharmacology 26 32259664
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
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 24 33710695
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
2019 13-HODE, 9-HODE and ALOX15 as potential players in Rett syndrome OxInflammation. Free radical biology & medicine 24 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 24 29702245
2015 Mutagenesis of triad determinants of rat Alox15 alters the specificity of fatty acid and phospholipid oxygenation. Archives of biochemistry and biophysics 24 25731857
2010 Selenoprotein P protects cells from lipid hydroperoxides generated by 15-LOX-1. Prostaglandins, leukotrienes, and essential fatty acids 24 20826080
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
2025 Lachnospiraceae-bacterium alleviates ischemia-reperfusion injury in steatotic donor liver by inhibiting ferroptosis via the Foxo3-Alox15 signaling pathway. Gut microbes 22 39882747
2024 FGF21 modulates immunometabolic homeostasis via the ALOX15/15-HETE axis in early liver graft injury. Nature communications 22 39362839
2023 Circadian clock protein Bmal1 accelerates acute myeloid leukemia by inhibiting ferroptosis through the EBF3/ALOX15 axis. Cancer science 22 37271497
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
2014 15-LOX-1 suppression of hypoxia-induced metastatic phenotype and HIF-1α expression in human colon cancer cells. Cancer medicine 21 24634093
2007 Polymorphisms in ALOX12, but not ALOX15, are significantly associated with BMD in postmenopausal women. Calcified tissue international 21 17520163
2024 Inhibition of SAT1 alleviates chondrocyte inflammation and ferroptosis by repressing ALOX15 expression and activating the Nrf2 pathway. Bone & joint research 20 38447596
2024 Alpha-tocopherol inhibits ferroptosis and promotes neural function recovery in rats with spinal cord injury via downregulating Alox15. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 20 38754264
2018 Inhibition of spinal 15-LOX-1 attenuates TLR4-dependent, nonsteroidal anti-inflammatory drug-unresponsive hyperalgesia in male rats. Pain 18 30130298
2023 S1PR1/S1PR3-YAP signaling and S1P-ALOX15 signaling contribute to an aggressive behavior in obesity-lymphoma. Journal of experimental & clinical cancer research : CR 17 36600310
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 17 35531094
2024 Identifying ALOX15-initiated lipid peroxidation increases susceptibility to ferroptosis in asthma epithelial cells. Biochimica et biophysica acta. Molecular basis of disease 16 38641013
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 Hypoxic cardiac fibroblasts from failing human hearts decrease cardiomyocyte beating frequency in an ALOX15 dependent manner. PloS one 15 30138423
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
2022 8-Geranyloxycarbostyril as a potent 15-LOX-1 inhibitor showed great anti-tumor effects against prostate cancer. Life sciences 14 35065164
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 Cerebroprotein hydrolysate-I ameliorates cognitive dysfunction in APP/PS1 mice by inhibiting ferroptosis via the p53/SAT1/ALOX15 signalling pathway. European journal of pharmacology 12 39032765
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 12 37354317
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
2024 Lactate-Dependent HIF1A Transcriptional Activation Exacerbates Severe Acute Pancreatitis Through the ACSL4/LPCAT3/ALOX15 Pathway Induced Ferroptosis. Journal of cellular biochemistry 11 39676583
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
2025 ALOX15 Aggravates Metabolic Dysfunction-Associated Steatotic Liver Disease in Mice with Type 2 Diabetes via Activating the PPARγ/CD36 Axis. Antioxidants & redox signaling 10 39815992
2024 Wogonin Alleviates DCD Liver Ischemia/Reperfusion Injury by Regulating ALOX15/iNOS-mediated Ferroptosis. Transplantation 10 38946036
2024 Chicoric acid acts as an ALOX15 inhibitor to prevent ferroptosis in asthma. International immunopharmacology 10 39298822
2021 Deletion of Alox15 improves kidney dysfunction and inhibits fibrosis by increased PGD2 in the kidney. Clinical and experimental nephrology 10 33595729
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 ALOX15-Driven Ferroptosis: The key target in Dihydrotanshinone I's epigenetic Battle in hepatic stellate cells against liver fibrosis. International immunopharmacology 9 39675198
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
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 9 32151768
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
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
2025 Wogonin attenuates septic cardiomyopathy by suppressing ALOX15-mediated ferroptosis. Acta pharmacologica Sinica 7 40205009
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
2024 SAT1/ALOX15 Signaling Pathway Is Involved in Ferroptosis After Skeletal Muscle Contusion. International journal of molecular sciences 7 39457099
2023 Silencing of ALOX15 reduces ferroptosis and inflammation induced by cerebral ischemia-reperfusion by regulating PHD2/HIF2α signaling pathway. Biotechnology & genetic engineering reviews 7 37154013
2023 Knock-in mice expressing a humanized arachidonic acid 15-lipoxygenase (Alox15) carry a partly dysfunctional erythropoietic system. Cellular & molecular biology letters 7 38030974
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 Silencing HEATR1 Rescues Cisplatin Resistance of Non-small Cell Lung Cancer by Inducing Ferroptosis via the p53/SAT1/ALOX15 Axis. Current cancer drug targets 6 38818906
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 6 38213304
2024 MAFB in Macrophages Regulates Prostaglandin E2-Mediated Lipid Mediator Class Switch through ALOX15 in Ischemic Acute Kidney Injury. Journal of immunology (Baltimore, Md. : 1950) 5 39230290