Affinage

GPX1

Glutathione peroxidase 1 · UniProt P07203

Length
203 aa
Mass
22.1 kDa
Annotated
2026-06-10
100 papers in source corpus 26 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GPX1 is a selenocysteine-containing glutathione peroxidase that detoxifies hydrogen peroxide and lipid hydroperoxides, serving as a central defense against acute oxidative stress in vivo (PMID:9126277, PMID:9712879). A single Gpx1 gene encodes both the cytosolic and mitochondrial enzyme, and its loss eliminates detectable GPX activity in both compartments (PMID:9126277). Genetic ablation renders mice hypersensitive to the oxidant paraquat and sensitizes neurons to H2O2-induced death (PMID:9712879), and GPX1-dependent peroxide removal is required for fibroblast proliferation and survival, where its loss provokes Cip1 elevation, NF-κB activation, and a senescence-like state (PMID:14732290). Across multiple tissues GPX1 is protective: it limits noise-induced cochlear damage (PMID:11545230), maintains lens gap junction coupling through connexin 46/50 levels and ion homeostasis (PMID:19067024), constrains pancreatic islet hydroperoxide accumulation and p53 phosphorylation (PMID:20586612), and restrains retinal neovascularization in oxygen-induced retinopathy (PMID:23287791); in the colon it acts redundantly with GPX2, since only the GPX1/GPX2 double knockout develops spontaneous ileocolitis (PMID:11518697). GPX1 modulates apoptotic balance by lowering the Bax/Bcl-2 ratio (PMID:16132718), and in selenium deficiency its loss elevates H2O2 to activate an NF-κB–AT1R axis driving renal sodium retention and hypertension (PMID:36868433). The enzyme is controlled at many levels: translation depends on selenocysteine UGA read-through that is impaired by homocysteine and suppressed by mTOR (PMID:15734734, PMID:24691473); transcription is driven by TFAP2C, RORα, and hypoxic HIF-1α (PMID:22964634, PMID:24597775, PMID:37572455); pre-mRNA splicing requires NONO/PSPC1 (PMID:35910786); promoter activity is silenced by DNMT2-mediated CpG methylation (PMID:22964634, PMID:35432721); and protein abundance is set by CUEDC2–TRIM33 and TRIM8 ubiquitin-mediated degradation as well as PPT1-regulated S-palmitoylation at Cys-76 and Cys-113 (PMID:27286733, PMID:35968584, PMID:39423458). Post-translationally, O-GlcNAcylation activates GPX1 and promotes its binding to c-Abl and Arg kinases (PMID:19944066).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1997 High

    Resolved whether the cytosolic and mitochondrial glutathione peroxidases derive from one gene, establishing the genetic identity of GPX1.

    Evidence Subcellular fractionation and enzyme activity assay in Gpx1 knockout vs wild-type mouse liver

    PMID:9126277

    Open questions at the time
    • Does not address differential targeting mechanism to mitochondria vs cytosol
    • Single tissue (liver) examined
  2. 1998 High

    Demonstrated that GPX1 is physiologically required to survive acute oxidant challenge, moving it from a biochemical activity to an in vivo protective enzyme.

    Evidence Paraquat lethality in Gpx1 knockout mice and H2O2 sensitivity of knockout cortical neurons

    PMID:9712879

    Open questions at the time
    • Does not define which downstream targets of peroxide damage are protected
    • Tissue-specific contributions not dissected
  3. 2001 High

    Revealed functional redundancy between GPX1 and GPX2 in the gut, explaining why single GPX1 loss is often phenotypically silent in some tissues.

    Evidence Spontaneous ileocolitis with elevated myeloperoxidase and lipid hydroperoxides only in Gpx1/Gpx2 double knockout mice

    PMID:11518697

    Open questions at the time
    • Relative contribution of each isoform not quantified
    • Mechanism linking peroxide accumulation to inflammation not detailed
  4. 2005 High

    Established that GPX1 abundance is controlled at the level of selenocysteine UGA read-through, identifying homocysteine as a translational inhibitor independent of mRNA.

    Evidence UGA-luciferase SECIS reporter and folate-antagonist manipulation of homocysteine with activity/protein/mRNA readouts

    PMID:15734734

    Open questions at the time
    • Molecular step in selenocysteine machinery targeted by homocysteine not pinpointed
    • In vivo relevance to disease states not tested here
  5. 2005 Medium

    Connected GPX1 to apoptotic regulation by showing it lowers the pro-apoptotic Bax/Bcl-2 ratio.

    Evidence GPX1 cDNA overexpression in ECV304 endothelial cells with Bax/Bcl-2/p53 RT-PCR and Western blot

    PMID:16132718

    Open questions at the time
    • Overexpression-only; loss-of-function not tested
    • Mechanism linking peroxide removal to Bax transcription unknown
  6. 2008 High

    Extended GPX1 function beyond classical antioxidant defense to maintaining lens gap junction coupling and ion homeostasis.

    Evidence Whole-lens impedance, ion imaging, and quantitative Western blot for Cx46/Cx50 in Gpx1 knockout lenses

    PMID:19067024

    Open questions at the time
    • Whether connexin loss is direct or oxidative-damage-mediated unresolved
    • Single-tissue specialization
  7. 2009 Medium

    Identified a post-translational activating modification, showing O-GlcNAcylation activates GPX1 and couples it to c-Abl/Arg kinase signaling under hyperglycemia.

    Evidence O-GlcNAc IP/site mapping, Co-IP with c-Abl and Arg, and in vivo NTZ-induced activation in mouse liver

    PMID:19944066

    Open questions at the time
    • Functional consequence of c-Abl/Arg binding not defined
    • Co-IP without reciprocal structural validation of the modification site
  8. 2010 Medium

    Distinguished H2O2- from superoxide-dependent control of pancreatic function, placing GPX1 specifically upstream of islet p53 activation and beta-cell mass.

    Evidence Islet hydroperoxide/superoxide measurement and p53 phosphorylation in GPX1 vs SOD1 knockout mice

    PMID:20586612

    Open questions at the time
    • Mechanism linking H2O2 to p53 phosphorylation not resolved
    • Single lab
  9. 2012 High

    Identified TFAP2C as a direct transcriptional activator of GPX1 and showed promoter CpG methylation silences GPX1 by blocking TFAP2C binding.

    Evidence ChIP-seq, TFAP2C knockdown, methylation analysis, and 5'-aza-dC demethylation in breast cancer cells

    PMID:22964634

    Open questions at the time
    • Whether TFAP2C regulation operates outside breast cancer not tested
    • Methylation-writing enzyme not identified here
  10. 2012 Medium

    Showed ZNF143 upregulates GPX1 activity and the selenocysteine synthesis pathway to support survival of respiration-defective cells.

    Evidence ZNF143/GPX1 knockdown, activity assays, and SepSecS expression in mitochondrial respiratory-defective cells

    PMID:23152058

    Open questions at the time
    • Direct ZNF143 promoter binding to GPX1 not demonstrated
    • Effect may be indirect via selenocysteine supply
  11. 2014 Medium

    Defined additional layers of GPX1 control: RORα as a transcriptional inducer and mTOR as a translational suppressor.

    Evidence RORα overexpression/agonist in hepatocytes with promoter element mapping; rapamycin protein/mRNA dissociation in CML cells

    PMID:24597775 PMID:24691473

    Open questions at the time
    • mTOR effect on selenocysteine machinery inferred, not mapped to a step
    • RORα element function not validated by mutation
  12. 2016 High

    Reconstituted a ubiquitin-degradation pathway for GPX1, showing CUEDC2 drives TRIM33-mediated degradation that limits cardiac ROS scavenging.

    Evidence Cuedc2 knockout mice, Co-IP of CUEDC2-TRIM33-GPX1, ubiquitination assay, and in vivo I/R infarct measurement

    PMID:27286733

    Open questions at the time
    • Ubiquitination site on GPX1 not mapped
    • Whether TRIM33 directly ubiquitinates GPX1 vs scaffolds another E3 unresolved
  13. 2017 Medium

    Showed GPX1-dependent reductive balance, rather than ROS removal alone, is required for chondrogenic differentiation.

    Evidence shRNA knockdown in ATDC5 cells with GSH/GSSG measurement and diamide-versus-NAC rescue

    PMID:28039148

    Open questions at the time
    • Molecular targets of reductive stress in chondrogenesis unknown
    • Single cell-line model
  14. 2017 Medium

    Demonstrated GPX1 can act non-cell-autonomously, being delivered via exosomes to confer antioxidant and hepatoprotective effects on recipient cells.

    Evidence GPX1 knockdown in donor hucMSCs and exosome administration in CCl4 liver injury model

    PMID:28089078

    Open questions at the time
    • Mechanism of GPX1 loading into exosomes not defined
    • Uptake/activity in recipient cells not quantified at enzyme level
  15. 2020 Medium

    Linked GPX1 to circadian and mitochondrial physiology via a direct interaction with the clock protein PER1 that enhances its activity.

    Evidence Co-IP of PER1-GPX1, Per1 knockout mice, and oxygen-consumption rhythm/GPx activity assays

    PMID:32896721

    Open questions at the time
    • How PER1 binding mechanistically enhances GPX1 activity unknown
    • Single Co-IP without reciprocal mapping of interaction interface
  16. 2021 Medium

    Placed GPX1 downstream of CCL5 signaling in neuronal ROS control relevant to traumatic brain injury recovery.

    Evidence CCL5 knockout TBI mice with GPX1 activity, behavioral testing, and recombinant CCL5/NAC rescue

    PMID:34315111

    Open questions at the time
    • Signaling steps linking CCL5 receptor to GPX1 expression not mapped
    • Whether CCL5 acts transcriptionally on GPX1 untested
  17. 2022 Medium

    Identified pre-mRNA splicing as a control point, with NONO/PSPC1 binding a GPX1 intron motif to ensure correct splicing and functional protein.

    Evidence RIP-PCR/RNA pulldown of NONO on GPX1 pre-mRNA and intron-retention readout in NONO-knockdown glioblastoma cells

    PMID:35910786

    Open questions at the time
    • Direct PSPC1 contribution not separated from NONO
    • Generality of splicing dependence beyond glioblastoma untested
  18. 2022 Medium

    Added DNMT2-mediated promoter methylation and TRIM8-mediated ubiquitination as repressive controls on GPX1 in cardiomyocytes, and showed selenium reverses the methylation arm.

    Evidence Bisulfite sequencing and selenium/AZA rescue (DNMT2); Co-IP, ubiquitination assay, and I/R epistasis (TRIM8)

    PMID:35432721 PMID:35968584

    Open questions at the time
    • TRIM8 ubiquitination site on GPX1 not mapped
    • Whether DNMT2 acts directly on the GPX1 promoter or via intermediaries unresolved
  19. 2023 High

    Established hypoxic induction of GPX1 by HIF-1α as a survival mechanism allowing tumor cells to detoxify hypoxia-driven H2O2, with exosomal GPX1 protecting neighboring cells.

    Evidence HIF-1α ChIP on GPX1 promoter, GPX1 knockdown with H2O2/apoptosis readouts, and glioblastoma xenografts

    PMID:37572455

    Open questions at the time
    • Whether the same axis operates in non-malignant hypoxic tissue not tested
    • Mechanism of GPX1 exosomal sorting not defined
  20. 2023 Medium

    Defined a GPX1/H2O2/NF-κB/AT1R pathway linking selenium-dependent GPX1 loss to renal sodium handling and hypertension.

    Evidence Selenium-deficient rats, GPX1 silencing, NF-κB inhibitor and ebselen interventions with AT1R/Na+-K+-ATPase readouts

    PMID:36868433

    Open questions at the time
    • Direct molecular link between H2O2 and p65 activation not specified
    • Single rodent model
  21. 2024 High

    Identified S-palmitoylation at Cys-76 and Cys-113 as a stability-regulating modification, with PPT1 depalmitoylation destabilizing GPX1 and modulating angiogenesis.

    Evidence Palmitoylation site mutagenesis, PPT1 knockout/overexpression and DC661 inhibition in an oxygen-induced retinopathy model

    PMID:39423458

    Open questions at the time
    • Palmitoyl-transferase adding the modification not identified
    • How palmitoylation alters GPX1 stability mechanistically unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the many transcriptional, translational, splicing, and post-translational controls of GPX1 are integrated to set enzyme dosage in a given cell type, and which are dominant in human disease, remains unresolved.
  • No unified quantitative model of GPX1 regulation across regulators
  • Structural basis of GPX1 modification sites and partner binding not defined
  • Most disease links rest on single-lab rodent or cell models

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016209 antioxidant activity 3 GO:0016491 oxidoreductase activity 3 GO:0140098 catalytic activity, acting on RNA 2
Localization
GO:0005739 mitochondrion 2 GO:0005829 cytosol 2
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-8953897 Cellular responses to stimuli 3
Partners
ARGC-ABLCUEDC2NONOPER1PPT1TRIM33TRIM8

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 Mitochondrial GPX1 is encoded by the Gpx1 gene. Gpx1 knockout mice show no detectable GPX activity in either cytosol or mitochondria of liver, establishing that the Gpx1 gene encodes both the cytosolic and mitochondrial forms of glutathione peroxidase. Subcellular fractionation (Percoll gradient) of Gpx1 knockout and wild-type mouse liver; enzyme activity assay with H2O2 and cumene hydroperoxide as substrates; electron microscopy to confirm fraction purity Archives of biochemistry and biophysics High 9126277
1998 GPX1 protects against acute oxidative stress in vivo: Gpx1 knockout mice are hypersensitive to the oxidant paraquat (100% lethality at doses non-lethal to wild-type) and cortical neurons from Gpx1 knockout mice are more susceptible to H2O2-induced cell death. In vivo paraquat challenge in Gpx1 (-/-) knockout mice; primary cortical neuron H2O2 exposure assay The Journal of biological chemistry High 9712879
2000 GPX1 loss increases noise-induced cochlear damage: Gpx1 knockout mice show significantly greater noise-induced hearing loss and increased cochlear hair cell and nerve fiber loss compared to wild-type controls, establishing a protective role of GPX1 in the cochlea. Auditory brainstem response (ABR) threshold measurement; cochlear histology in Gpx1 knockout mice after broadband noise exposure Journal of the Association for Research in Otolaryngology : JARO Medium 11545230
2001 Combined deficiency of GPX1 and GPX2 (double knockout) causes spontaneous inflammatory bowel disease with ileocolitis, elevated myeloperoxidase activity, and lipid hydroperoxides in the colon mucosa, whereas single knockouts of either Gpx1 or Gpx2 alone do not produce this phenotype under standard conditions. Genetic double-knockout mouse model; histological examination; myeloperoxidase activity assay; lipid hydroperoxide measurement American journal of physiology. Gastrointestinal and liver physiology High 11518697
2004 GPX1 deficiency leads to senescence-like changes in fibroblasts, including reduced proliferative capacity, elevated Cip1 levels, increased NF-κB activation, and increased susceptibility to H2O2-induced apoptosis, demonstrating that GPX1-mediated H2O2 removal is required for normal cell cycle progression and survival. Fibroblasts derived from Gpx1 knockout mice; proliferation assays; DNA synthesis measurement; Western blotting for Cip1; NF-κB activation assay; dose-response H2O2 apoptosis assay Free radical biology & medicine Medium 14732290
2005 Homocysteine decreases GPX1 protein expression and activity by inhibiting the selenocysteine incorporation mechanism required for translating the UGA codon, without affecting GPX1 mRNA levels. This was shown using a UGA-luciferase reporter containing GPX1 or GPX3 SECIS elements. Luciferase UGA read-through reporter assay with GPX1/GPX3 SECIS elements; folate antagonist (aminopterin/HAT/Met) treatment to elevate cellular homocysteine; enzyme activity assay; quantitative mRNA and protein measurement The Journal of biological chemistry High 15734734
2005 GPX1 overexpression reduces Bax mRNA and protein levels (by ~43-46%) without affecting Bcl-2 or p53 levels in endothelial cells, thereby lowering the Bax/Bcl-2 apoptotic ratio at baseline. Stable transfection of GPX1 cDNA in ECV304 endothelial cells; quantitative RT-PCR; Western blot for Bax, Bcl-2, and p53 Molecular and cellular biochemistry Medium 16132718
2008 GPX1 knockout reduces gap junction coupling conductance in the lens (72% of normal in outer fibers, 45% in inner core), reduces connexin 46 and connexin 50 protein levels by ~50%, and causes accumulation of Ca2+ and Na+ in the lens core, establishing GPX1 as required for normal lens gap junction function. Whole-lens impedance studies; osmotic swelling of fiber cell membrane vesicles; Fura-2 and SBFI microinjection to measure [Ca2+]i and [Na+]i; quantitative Western blot for Cx46, Cx50, and AQP0 The Journal of membrane biology High 19067024
2009 GPX1 is O-GlcNAc modified on its C-terminus under hyperglycemic conditions, and this O-GlcNAcylation is required for GPX1 activation and for GPX1 binding to c-Abl and Arg kinases. Pharmacological increase of O-GlcNAc in vivo (using the O-GlcNAcase inhibitor NTZ) induces GPX1 activation in mouse liver. O-GlcNAc immunoprecipitation and site mapping; co-immunoprecipitation of GPX1 with c-Abl and Arg; in vivo NTZ injection in mice with GPX1 activity measurement Biochemical and biophysical research communications Medium 19944066
2010 GPX1 knockout specifically elevates islet hydroperoxide levels and upregulates p53 phosphorylation, and GPX1-deficient mice show decreased plasma insulin and reduced islet β-cell mass without blocking glucose-stimulated insulin secretion (in contrast to SOD1 knockout), establishing a distinct role of H2O2 vs. superoxide in pancreatic function. GPX1 single and double knockout mouse models; islet superoxide and hydroperoxide measurements; blood glucose and plasma insulin assays; p53 phosphorylation Western blot; epistasis with SOD1 knockout Antioxidants & redox signaling Medium 20586612
2012 The transcription factor TFAP2C (but not TFAP2A) directly binds an AP-2 regulatory element in the GPX1 promoter and is required for GPX1 expression. GPX1 promoter CpG island methylation prevents TFAP2C binding, and demethylation with 5'-aza-dC restores TFAP2C binding and GPX1 expression. ChIP-seq for TFAP2C in breast cancer cell lines; TFAP2C knockdown with measurement of GPX1 mRNA/protein; GPX1 promoter methylation analysis; 5'-aza-dC treatment and ChIP; GPX1 overexpression with t-butyl hydroperoxide resistance assay Oncogene High 22964634
2012 ZNF143 transcription factor upregulates GPX1 activity in mitochondrial respiratory-defective cells, promoting cell survival under oxidative stress. ZNF143 also activates SepSecS (required for selenocysteine tRNA synthesis), increasing the selenocysteine synthesis pathway. ZNF143 and GPX1 knockdown in mitochondrial respiratory-defective cells; GPX1 activity assay; measurement of GSH, GCLC, GCLM, and SepSecS expression; cisplatin sensitivity assay Cell death & disease Medium 23152058
2013 GPX1 deficiency exacerbates retinopathy of prematurity: GPX1 knockout mice exposed to hyperoxia-hypoxia show larger retinal avascular areas, increased neovascularization, elevated VEGF expression, increased nitrotyrosine, and increased superoxide compared to wild-type ROP mice. GPX1 knockout mice in oxygen-induced retinopathy model; retinal histology; qRT-PCR for VEGF; immunolabeling for nitrotyrosine and superoxide Investigative ophthalmology & visual science Medium 23287791
2014 RORα (retinoic acid-related orphan receptor α) transcriptionally induces GPX1 expression through RORα response elements located in the upstream promoter of the Gpx1 gene, thereby reducing hepatic oxidative stress. RORα overexpression and cholesterol sulfate (agonist) treatment in primary hepatocytes; qRT-PCR measurement of GPX1 mRNA; promoter analysis identifying RORα response elements Antioxidants & redox signaling Medium 24597775
2014 GPX1 translation is regulated by the mTOR pathway: rapamycin (mTOR inhibitor) elevates GPX1 protein levels independently of mRNA levels, indicating mTOR suppresses selenocysteine-containing GPX1 translation. Treatment of CML cell lines with rapamycin; GPX1 protein quantification by Western blot; mRNA steady-state level measurement PloS one Medium 24691473
2016 CUEDC2 promotes TRIM33-mediated ubiquitination and proteasomal degradation of GPX1, suppressing GPX1 protein levels in cardiomyocytes. Loss of CUEDC2 increases GPX1 protein, enhances ROS scavenging, and reduces infarct size after ischemia/reperfusion injury. Cuedc2 knockout mice; Co-IP to show CUEDC2–TRIM33 and TRIM33–GPX1 interactions; ubiquitination assay; Western blot for GPX1; in vivo I/R injury model with infarct size measurement EMBO molecular medicine High 27286733
2017 GPX1 knockdown in ATDC5 chondrogenic cells impairs chondrogenic differentiation (reduced Sox9, collagen II, aggrecan expression; reduced GAG accumulation) primarily through induction of reductive stress (elevated GSH/GSSG ratio) rather than through antioxidant ROS removal, as the impaired chondrogenesis was rescued by the thiol-oxidizing agent diamide but not by the antioxidant NAC. shRNA-mediated GPX1 knockdown in ATDC5 cells; measurement of ROS, GSH/GSSG ratio; alcian blue staining for GAGs; rescue experiments with diamide (thiol-oxidizer) and NAC Acta biochimica et biophysica Sinica Medium 28039148
2017 hucMSC exosome-derived GPX1 protein is delivered to recipient hepatocytes and is required for the antioxidant and hepatoprotective effects of these exosomes; knockdown of GPX1 in donor hucMSCs abrogates the antioxidant and anti-apoptotic capacity of the exosomes both in vitro and in vivo. GPX1 knockdown in hucMSCs; exosome isolation and administration in CCl4 liver injury mouse model; measurement of oxidative stress markers, apoptosis, and liver function in vitro and in vivo Molecular therapy Medium 28089078
2020 PER1 physically interacts with GPX1 in the cytoplasm and enhances GPX1 activity, thereby improving mitochondrial oxidative phosphorylation efficiency. Per1 deficiency impairs daily mitochondrial dynamics and deregulates cellular GPx-related ROS fluctuations in peripheral organs. Co-immunoprecipitation (PER1/GPX1 interaction); Per1 knockout mice; oxygen consumption rhythm measurement; GPx activity assay; mitochondrial function assays Redox biology Medium 32896721
2021 CCL5 signaling increases GPX1 expression and reduces intracellular ROS in neurons; CCL5 knockout mice after mild TBI show reduced GPX1 activity, increased ROS, and impaired hippocampal memory recovery that can be rescued by intranasal recombinant CCL5 or N-acetylcysteine. CCL5 knockout mice with weight-drop TBI model; behavioral testing (Novel object recognition, Barnes Maze); NADPH oxidase activity; GPX1 activity assay; GPX1 overexpression in SHSY5Y cells; NAC and recombinant CCL5 rescue Redox biology Medium 34315111
2022 The splicing factor NONO, in association with PSPC1, binds a consensus motif in the intron of GPX1 pre-mRNA and promotes its correct splicing. NONO knockdown causes GPX1 intron retention, reducing functional GPX1 protein, impairing redox homeostasis and promoting apoptosis in glioblastoma cells. RNA sequencing of NONO-knockdown GBM cells; RIP-PCR and RNA pulldown to show NONO binding to GPX1 pre-mRNA intron; JC-1 staining and Seahorse assay for redox homeostasis; in vivo orthotopic xenograft model Theranostics Medium 35910786
2022 DNMT2-mediated DNA methylation of the GPX1 promoter reduces GPX1 expression in AGE-exposed cardiomyocytes; selenium supplementation suppresses DNMT2 expression, reduces GPX1 promoter methylation, restores GPX1 expression/activity, and protects against AGE-induced cardiac dysfunction. Rat primary myocyte exposure to AGEs; bisulfite sequencing PCR of GPX1 promoter; DNMT inhibitor (AZA) and selenium supplementation; GPX1 activity and protein measurements; cardiac function evaluation in rat model Oxidative medicine and cellular longevity Medium 35432721
2022 TRIM8 protein interacts with GPX1 and promotes GPX1 ubiquitination, leading to reduced GPX1 protein levels in cardiomyocytes; TRIM8 knockdown partially alleviates I/R-induced cardiomyocyte injury, and GPX1 knockdown abolishes the cardioprotective effect of salvianolic acid B. Co-IP of TRIM8 and GPX1; ubiquitination assay; TRIM8 knockdown/overexpression in AC16 cardiomyocytes; GPX1 knockdown rescue experiment; in vivo rat I/R model Pharmaceutical biology Medium 35968584
2023 HIF-1α binds directly to the GPX1 promoter under hypoxic conditions to increase GPX1 expression, enabling glioblastoma cells to detoxify excess H2O2 caused by hypoxia. GPX1 depletion causes H2O2 overload and apoptosis in glioblastoma cells, and hypoxia also increases exosomal GPX1 that protects adjacent cells from H2O2 or radiation-induced apoptosis. HIF-1α ChIP on GPX1 promoter; GPX1 knockdown in glioblastoma cells; H2O2 measurement; apoptosis assay; exosome isolation and functional assays; glioblastoma xenograft model Redox biology High 37572455
2023 GPX1 deficiency increases H2O2 levels that activate NF-κB p65, which upregulates renal angiotensin II type 1 receptor (AT1R) expression, causing sodium retention and hypertension in selenium-deficient rats. Ebselen (GPX1 mimetic), GPX1 silencing + NF-κB inhibitor (PDTC) experiments confirmed the GPx1/H2O2/NF-κB/AT1R pathway. Selenium-deficient rat model; GPx1 silencing in renal proximal tubule cells; NF-κB inhibitor PDTC; ebselen treatment; AT1R expression and Na+-K+-ATPase activity measurements; nuclear translocation of NF-κB p65 Free radical biology & medicine Medium 36868433
2024 GPX1 undergoes S-palmitoylation at cysteine residues 76 and 113; PPT1 (palmitoyl-protein thioesterase 1) mediates GPX1 depalmitoylation and reduces GPX1 protein stability. Inhibiting GPX1 palmitoylation (via PPT1 expression or non-palmitoylated mutant) enhances neovascular angiogenesis, while enhancing palmitoylation (PPT1 inhibition with DC661) suppresses retinal angiogenesis in an oxygen-induced retinopathy model. Palmitoylation site mapping at Cys-76 and Cys-113 by mutagenesis; PPT1 knockout and overexpression; non-palmitoylated Gpx1 mutant expression; oxygen-induced retinopathy mouse model; angiogenesis assays Redox biology High 39423458

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Mice with a homozygous null mutation for the most abundant glutathione peroxidase, Gpx1, show increased susceptibility to the oxidative stress-inducing agents paraquat and hydrogen peroxide. The Journal of biological chemistry 354 9712879
2017 hucMSC Exosome-Derived GPX1 Is Required for the Recovery of Hepatic Oxidant Injury. Molecular therapy : the journal of the American Society of Gene Therapy 266 28089078
2001 Mice with combined disruption of Gpx1 and Gpx2 genes have colitis. American journal of physiology. Gastrointestinal and liver physiology 236 11518697
2000 Targeted mutation of the gene for cellular glutathione peroxidase (Gpx1) increases noise-induced hearing loss in mice. Journal of the Association for Research in Otolaryngology : JARO 168 11545230
1997 The Gpx1 gene encodes mitochondrial glutathione peroxidase in the mouse liver. Archives of biochemistry and biophysics 127 9126277
2010 Loss of GPx2 increases apoptosis, mitosis, and GPx1 expression in the intestine of mice. Free radical biology & medicine 105 20828612
2005 Homocysteine down-regulates cellular glutathione peroxidase (GPx1) by decreasing translation. The Journal of biological chemistry 104 15734734
2015 Manganese superoxide dismutase (SOD2/MnSOD)/catalase and SOD2/GPx1 ratios as biomarkers for tumor progression and metastasis in prostate, colon, and lung cancer. Free radical biology & medicine 103 25866291
2010 Antiatherosclerotic and renoprotective effects of ebselen in the diabetic apolipoprotein E/GPx1-double knockout mouse. Diabetes 100 20823099
2007 Selenium and GPx-1 overexpression protect mammalian cells against UV-induced DNA damage. Biological trace element research 84 17625244
2008 Glutathione peroxidase 1 (GPX1) genetic polymorphism, erythrocyte GPX activity, and prostate cancer risk. International urology and nephrology 82 18563616
2022 Glutathione Peroxidase GPX1 and Its Dichotomous Roles in Cancer. Cancers 80 35626163
2010 Knockouts of SOD1 and GPX1 exert different impacts on murine islet function and pancreatic integrity. Antioxidants & redox signaling 76 20586612
2009 Association between GPx1 Pro198Leu polymorphism, GPx1 activity and plasma selenium concentration in humans. European journal of nutrition 76 19415410
2003 An imbalance in antioxidant defense affects cellular function: the pathophysiological consequences of a reduction in antioxidant defense in the glutathione peroxidase-1 (Gpx1) knockout mouse. Redox report : communications in free radical research 74 12804009
2014 RORα decreases oxidative stress through the induction of SOD2 and GPx1 expression and thereby protects against nonalcoholic steatohepatitis in mice. Antioxidants & redox signaling 70 24597775
2009 GPX1 Pro(198)Leu polymorphism, erythrocyte GPX activity, interaction with alcohol consumption and smoking, and risk of colorectal cancer. Mutation research 68 19428376
2004 Genetic variants of GPX1 and SOD2 and breast cancer risk at the Ontario site of the Breast Cancer Family Registry. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 67 14744747
2015 MicroRNA-153/Nrf-2/GPx1 pathway regulates radiosensitivity and stemness of glioma stem cells via reactive oxygen species. Oncotarget 65 26124081
2004 Fibroblasts derived from Gpx1 knockout mice display senescent-like features and are susceptible to H2O2-mediated cell death. Free radical biology & medicine 61 14732290
2020 Simultaneous detection of the enzyme activities of GPx1 and GPx4 guide optimization of selenium in cell biological experiments. Redox biology 60 32278283
2000 Low glutathione peroxidase activity in Gpx1 knockout mice protects jejunum crypts from gamma-irradiation damage. American journal of physiology. Gastrointestinal and liver physiology 57 10915653
2014 X-Ray fluorescence imaging and other analyses identify selenium and GPX1 as important in female reproductive function. Metallomics : integrated biometal science 53 25362850
2005 Allelic loss of the gene for the GPX1 selenium-containing protein is a common event in cancer. The Journal of nutrition 51 16317164
2022 Targeting the splicing factor NONO inhibits GBM progression through GPX1 intron retention. Theranostics 49 35910786
2013 Molecular cloning and characterization of cat, gpx1 and Cu/Zn-sod genes in pengze crucian carp (Carassius auratus var. Pengze) and antioxidant enzyme modulation induced by hexavalent chromium in juveniles. Comparative biochemistry and physiology. Toxicology & pharmacology : CBP 49 23462276
2012 Transcriptional regulation of the GPX1 gene by TFAP2C and aberrant CpG methylation in human breast cancer. Oncogene 48 22964634
2004 The salt-stress signal transduction pathway that activates the gpx1 promoter is mediated by intracellular H2O2, different from the pathway induced by extracellular H2O2. Plant physiology 46 15247370
2014 Association of Superoxide dismutases (SOD1 and SOD2) and Glutathione peroxidase 1 (GPx1) gene polymorphisms with type 2 diabetes mellitus. Free radical research 45 25283363
2013 Lack of the antioxidant glutathione peroxidase-1 (GPx1) exacerbates retinopathy of prematurity in mice. Investigative ophthalmology & visual science 43 23287791
2021 CCL5 via GPX1 activation protects hippocampal memory function after mild traumatic brain injury. Redox biology 41 34315111
2020 PER1 interaction with GPX1 regulates metabolic homeostasis under oxidative stress. Redox biology 41 32896721
2014 High GPX1 expression promotes esophageal squamous cell carcinoma invasion, migration, proliferation and cisplatin-resistance but can be reduced by vitamin D. International journal of clinical and experimental medicine 41 25356106
2014 Supplementing culture and vitrification-warming media with l-ascorbic acid enhances survival rates and redox status of IVP porcine blastocysts via induction of GPX1 and SOD1 expression. Cryobiology 39 24657197
2015 Pyrrolidine Dithiocarbamate Inhibits NF-KappaB Activation and Upregulates the Expression of Gpx1, Gpx4, Occludin, and ZO-1 in DSS-Induced Colitis. Applied biochemistry and biotechnology 38 26386585
2015 Glutathione peroxidase-1 gene (GPX1) variants, oxidative stress and risk of kidney complications in people with type 1 diabetes. Metabolism: clinical and experimental 37 26773925
2014 CAT, GPX1, MnSOD, GSTM1, GSTT1, and GSTP1 genetic polymorphisms in chronic myeloid leukemia: a case-control study. Oxidative medicine and cellular longevity 37 25436036
2010 GPX1 Pro198Leu polymorphism and breast cancer risk: a meta-analysis. Breast cancer research and treatment 37 20306294
2005 Overexpression of human GPX1 modifies Bax to Bcl-2 apoptotic ratio in human endothelial cells. Molecular and cellular biochemistry 37 16132718
2023 Cellular and exosomal GPx1 are essential for controlling hydrogen peroxide balance and alleviating oxidative stress in hypoxic glioblastoma. Redox biology 35 37572455
2008 The effects of GPX-1 knockout on membrane transport and intracellular homeostasis in the lens. The Journal of membrane biology 35 19067024
2022 Selenium Supplementation Improved Cardiac Functions by Suppressing DNMT2-Mediated GPX1 Promoter DNA Methylation in AGE-Induced Heart Failure. Oxidative medicine and cellular longevity 32 35432721
2013 The impact of GPX1 on the association of groundwater selenium and depression: a Project FRONTIER study. BMC psychiatry 31 23289525
2009 CAT C-262T and GPX1 Pro198Leu polymorphisms in a Turkish population. Molecular biology reports 31 19424819
2021 The Antioxidant Role of Selenium via GPx1 and GPx4 in LPS-Induced Oxidative Stress in Bovine Endometrial Cells. Biological trace element research 30 33895964
2017 Association of GPX1 and GPX4 polymorphisms with episodic memory and Alzheimer's disease. Neuroscience letters 30 29246792
2016 Oleuropein protects L-02 cells against H2O2-induced oxidative stress by increasing SOD1, GPx1 and CAT expression. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 30 27914828
2006 [Effects of oxidative DNA damage and genetic polymorphism of the glutathione peroxidase 1 (GPX1) and 8-oxoguanine glycosylase 1 (hOGG1) on lung cancer]. Journal of preventive medicine and public health = Yebang Uihakhoe chi 30 16615267
2023 Selenium deficiency causes hypertension by increasing renal AT1 receptor expression via GPx1/H2O2/NF-κB pathway. Free radical biology & medicine 29 36868433
2012 ZNF143 transcription factor mediates cell survival through upregulation of the GPX1 activity in the mitochondrial respiratory dysfunction. Cell death & disease 29 23152058
2010 Colitis locus on chromosome 2 impacting the severity of early-onset disease in mice deficient in GPX1 and GPX2. Inflammatory bowel diseases 29 20872835
2011 Association of GPX1 polymorphism, GPX activity and prostate cancer risk. Human & experimental toxicology 28 21636625
2020 LncRNA VPS9D1-AS1 promotes cell proliferation in acute lymphoblastic leukemia through modulating GPX1 expression by miR-491-5p and miR-214-3p evasion. Bioscience reports 27 32808668
2018 Association between Polymorphisms of Antioxidant Gene (MnSOD, CAT, and GPx1) and Risk of Coronary Artery Disease. BioMed research international 27 30225256
2010 The antioxidant enzyme GPX1 gene polymorphisms are associated with low BMD and increased bone turnover markers. Disease markers 26 21045266
2016 1,25-Dihydroxyvitamin D3 alleviates salivary adenoid cystic carcinoma progression by suppressing GPX1 expression through the NF-κB pathway. International journal of oncology 25 26782341
2011 GSTM1, GSTT1 null variants, and GPX1 single nucleotide polymorphism are not associated with bladder cancer risk in Egypt. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 25 21586620
2003 Overexpression of cytosolic glutathione peroxidase (GPX1) delays endothelial cell growth and increases resistance to toxic challenges. Biochimie 25 12829378
2002 Differential expression of glutathione reductase and cytosolic glutathione peroxidase, GPX1, in developing rat lungs and kidneys. Free radical research 25 12516874
2024 Selenium nanoparticles ameliorate lumbar disc degeneration by restoring GPX1-mediated redox homeostasis and mitochondrial function of nucleus pulposus cells. Journal of nanobiotechnology 24 39420311
2023 Selenium-modified bone cement promotes osteoporotic bone defect repair in ovariectomized rats by restoring GPx1-mediated mitochondrial antioxidant functions. Regenerative biomaterials 24 36852397
2022 Matrine inhibits advanced glycation end products-induced macrophage M1 polarization by reducing DNMT3a/b-mediated DNA methylation of GPX1 promoter. European journal of pharmacology 24 35597264
2013 The rs1050450 C > T polymorphism of GPX1 is associated with the risk of bladder but not prostate cancer: evidence from a meta-analysis. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 24 23975365
2012 Genetic variation in GPX1 is associated with GPX1 activity in a comprehensive analysis of genetic variations in selenoenzyme genes and their activity and oxidative stress in humans. The Journal of nutrition 23 22259188
2024 Se Alleviated Pb-Caused Neurotoxicity in Chickens: SPS2-GPx1-GSH-IL-2/IL-17-NO Pathway, Selenoprotein Suppression, Oxidative Stress, and Inflammatory Injury. Antioxidants (Basel, Switzerland) 22 38539903
2024 Polystyrene microplastics trigger testosterone decline via GPX1. The Science of the total environment 22 38977086
2022 Ginsenoside Re attenuates memory impairments in aged Klotho deficient mice via interactive modulations of angiotensin II AT1 receptor, Nrf2 and GPx-1 gene. Free radical biology & medicine 22 35840016
2021 Isothiocyanate Iberin inhibits cell proliferation and induces cell apoptosis in the progression of ovarian cancer by mediating ROS accumulation and GPX1 expression. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 22 34148735
2014 Evaluation of some antioxidant enzyme activities (SOD and GPX) and their polymorphisms (MnSOD2 Ala9Val, GPX1 Pro198Leu) in fibromyalgia. European review for medical and pharmacological sciences 22 24817295
2024 Enhancing Gpx1 palmitoylation to inhibit angiogenesis by targeting PPT1. Redox biology 20 39423458
2014 Translational regulation of GPx-1 and GPx-4 by the mTOR pathway. PloS one 19 24691473
2013 The effects of selenium and the GPx-1 selenoprotein on the phosphorylation of H2AX. Biochimica et biophysica acta 19 23518201
2021 Crocin Improves Endothelial Mitochondrial Dysfunction via GPx1/ROS/KCa3.1 Signal Axis in Diabetes. Frontiers in cell and developmental biology 18 33777959
2011 Association between genetic variants in glutathione peroxidase 1 (GPx1) gene, GPx activity and the risk of prostate cancer. Minerva urologica e nefrologica = The Italian journal of urology and nephrology 18 21993316
2009 O-GlcNAcylation regulates hyperglycemia-induced GPX1 activation. Biochemical and biophysical research communications 18 19944066
2017 GPx1 knockdown suppresses chondrogenic differentiation of ATDC5 cells through induction of reductive stress. Acta biochimica et biophysica Sinica 17 28039148
2010 Lipopolysaccharide-induced hepatic oxidative injury is not potentiated by knockout of GPX1 and SOD1 in mice. Biochemical and biophysical research communications 17 21145306
2023 Variability in oxidative stress-related genes (SOD2, CAT, GPX1, GSTP1, NOS3, NFE2L2, and UCP2) and susceptibility to migraine clinical phenotypes and features. Frontiers in neurology 16 36698892
2023 Selenium-ruthenium complex blocks H1N1 influenza virus-induced cell damage by activating GPx1/TrxR1. Theranostics 16 37064873
2022 Glutathione Regulates GPx1 Expression during CA1 Neuronal Death and Clasmatodendrosis in the Rat Hippocampus following Status Epilepticus. Antioxidants (Basel, Switzerland) 16 35453441
2022 Salvianolic acid B inhibits myocardial I/R-induced ROS generation and cell apoptosis by regulating the TRIM8/GPX1 pathway. Pharmaceutical biology 16 35968584
2022 The Association of Polymorphisms in Genes Encoding Antioxidant Enzymes GPX1 (rs1050450), SOD2 (rs4880) and Transcriptional Factor Nrf2 (rs6721961) with the Risk and Development of Prostate Cancer. Medicina (Kaunas, Lithuania) 16 36295574
2017 The role of GPX1 in the pathogenesis of female pelvic organ prolapse. PloS one 16 28783735
2016 Genetic overexpressing of GPx-1 attenuates cocaine-induced renal toxicity via induction of anti-apoptotic factors. Clinical and experimental pharmacology & physiology 16 26850368
2016 Influence of Gender and SNPs in GPX1 Gene on Biomarkers of Selenium Status in Healthy Brazilians. Nutrients 16 27164132
2016 CUEDC2 modulates cardiomyocyte oxidative capacity by regulating GPX1 stability. EMBO molecular medicine 16 27286733
2012 GPX1 gene Pro200Leu polymorphism, erythrocyte GPX activity, and cancer risk. Molecular biology reports 16 23073788
2005 Association between polymorphisms of the GPX1 gene and second primary tumours after index squamous cell cancer of the head and neck. Oral oncology 16 15878749
2002 Down-regulation of GPx1 mRNA and the loss of GPx1 activity causes cellular damage in the liver of selenium-deficient rabbits. Journal of animal physiology and animal nutrition 16 12452969
2024 Translational selenium nanoparticles boost GPx1 activation to reverse HAdV-14 virus-induced oxidative damage. Bioactive materials 15 38745588
2018 Sodium selenite inhibits deoxynivalenol-induced injury in GPX1-knockdown porcine splenic lymphocytes in culture. Scientific reports 15 30518949
2015 DNA damage and oxidative stress response to selenium yeast in the non-smoking individuals: a short-term supplementation trial with respect to GPX1 and SEPP1 polymorphism. European journal of nutrition 15 26658762
2010 Dietary carotenoid-rich oil supplementation improves exercise-induced anisocytosis in runners: influences of haptoglobin, MnSOD (Val9Ala), CAT (21A/T) and GPX1 (Pro198Leu) gene polymorphisms in dilutional pseudoanemia (sports anemia). Genetics and molecular biology 15 21637495
2009 Regulatory mechanism for expression of GPX1 in response to glucose starvation and Ca in Saccharomyces cerevisiae: involvement of Snf1 and Ras/cAMP pathway in Ca signaling. Genes to cells : devoted to molecular & cellular mechanisms 15 20002498
2007 Gpx1 is a stationary phase-specific thioredoxin peroxidase in fission yeast. Biochemical and biophysical research communications 15 18162174
2021 Genetic variations of three important antioxidative enzymes SOD2, CAT, and GPX1 in nonalcoholic steatohepatitis. Journal of the Chinese Medical Association : JCMA 14 33009206
2019 GPx1-mediated DNMT1 expression is involved in the blocking effects of selenium on OTA-induced cytotoxicity and DNA damage. International journal of biological macromolecules 14 31790739
2019 Toxicity of DON on GPx1-Overexpressed or Knockdown Porcine Splenic Lymphocytes In Vitro and Protective Effects of Sodium Selenite. Oxidative medicine and cellular longevity 13 30944693
2009 Lack of association of GPX1 and MnSOD genes with symptom severity and response to clozapine treatment in schizophrenia subjects. Human psychopharmacology 13 19946932
2004 No association between the Pro197Leu polymorphism in the glutathione peroxidase (GPX1) gene and schizophrenia. Psychiatric genetics 13 15318035

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