Affinage

GPX1

Glutathione peroxidase 1 · UniProt P07203

Length
203 aa
Mass
22.1 kDa
Annotated
2026-04-28
100 papers in source corpus 20 papers cited in narrative 20 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GPX1 is a selenocysteine-containing glutathione peroxidase that serves as a primary intracellular scavenger of hydrogen peroxide and organic hydroperoxides, protecting cells against oxidative stress-induced apoptosis, senescence, and ischemia-reperfusion injury (PMID:9712879, PMID:14732290, PMID:27286733). Encoded by a single gene that supplies both cytosolic and mitochondrial pools (PMID:9126277), GPX1 modulates downstream signaling by suppressing NF-κB activation through preferential inhibition of IKKα (PMID:11491654) and sustaining PI3K-Akt pro-survival signaling in neurons (PMID:15663476). GPX1 expression is controlled transcriptionally by TFAP2C and HIF-1α (with promoter CpG methylation acting as a silencer) (PMID:22964634, PMID:37572455), translationally through SECIS-dependent selenocysteine insertion that is suppressed by homocysteine and enhanced by mTOR inhibition (PMID:15734734, PMID:24691473), at the splicing level by NONO/PSPC1 (PMID:35910786), and post-translationally by O-GlcNAcylation (activating, enabling c-Abl/Arg interaction), S-palmitoylation at C76/C113 (stabilizing, opposed by PPT1), and CUEDC2–TRIM33-mediated ubiquitin-proteasomal degradation (PMID:19944066, PMID:39423458, PMID:27286733).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1997 High

    Establishing that cytosolic and mitochondrial GPX activities arise from the same gene resolved the question of whether separate genes encoded compartment-specific isoforms.

    Evidence Subcellular fractionation and GPX activity assays in Gpx1 knockout versus wild-type mouse liver

    PMID:9126277

    Open questions at the time
    • Mechanism of GPX1 dual targeting (mitochondrial import signal usage) not characterized
    • Relative contribution of mitochondrial vs. cytosolic pools to antioxidant defense not quantified
  2. 1998 High

    Demonstrating that Gpx1 knockout mice are hypersensitive to paraquat and H2O2 established GPX1 as a physiologically essential antioxidant enzyme in vivo.

    Evidence Gpx1 knockout mice challenged with paraquat (lethality) and primary cortical neurons treated with H2O2 (cell death)

    PMID:9712879

    Open questions at the time
    • Relative contribution of GPX1 versus other peroxidases (GPX4, catalase, peroxiredoxins) not delineated
    • Tissue-specific vulnerability to GPX1 loss not systematically mapped
  3. 2001 Medium

    Linking GPX1 to NF-κB suppression via selective IKKα inhibition revealed a specific signaling node downstream of H2O2 clearance, beyond bulk ROS detoxification.

    Evidence Adenoviral GPX1 overexpression with dominant-negative IKKα/IKKβ, NF-κB reporter and EMSA

    PMID:11491654

    Open questions at the time
    • Direct physical interaction between GPX1 and IKKα not demonstrated
    • Whether GPX1 modifies a specific cysteine on IKKα is unknown
  4. 2005 Medium

    Showing that Gpx1 knockout neurons have diminished Akt phosphorylation after oxidative challenge and ischemia-reperfusion placed GPX1 upstream of the PI3K-Akt survival axis in the brain.

    Evidence Primary Gpx1−/− neurons, H2O2 challenge, PI3K inhibitor epistasis, phospho-Akt western blot, MCAO ischemia model

    PMID:15663476

    Open questions at the time
    • Whether GPX1 acts directly on a PI3K/PTEN redox switch or indirectly via bulk peroxide clearance is unresolved
    • Overexpression studies in MCF-7 showed opposite direction on Akt, raising context-dependency questions
  5. 2005 High

    Identifying homocysteine as a translational suppressor of GPX1 through impaired SECIS-dependent selenocysteine insertion revealed a metabolite-level regulatory mechanism linking one-carbon metabolism to selenoprotein production.

    Evidence SECIS-luciferase reporter, enzymatic activity assay, western blot, folate antagonist to raise homocysteine

    PMID:15734734

    Open questions at the time
    • Identity of the molecular target of homocysteine within the SECIS/translational machinery not pinpointed
    • In vivo relevance in hyperhomocysteinemic patients not confirmed
  6. 2009 Medium

    Discovery that O-GlcNAcylation of GPX1 is required for enzymatic activation and for binding c-Abl/Arg kinases established a post-translational switch linking glucose metabolism to antioxidant capacity.

    Evidence Co-immunoprecipitation, O-GlcNAcase inhibitor injection, GPX activity assay, glycosylation analysis

    PMID:19944066

    Open questions at the time
    • Exact O-GlcNAcylated residue(s) not mapped
    • Functional consequence of c-Abl/Arg binding on GPX1 activity or localization not determined
  7. 2011 High

    Demonstrating that SOD1 deficiency causes oxidative conversion of the GPX1 active-site selenocysteine to dehydroalanine revealed a direct chemical interdependence between the two antioxidant enzymes.

    Evidence Mass spectrometry of GPX1 active-site residue in Sod1−/− mice, kinetic analysis, tetramer structure

    PMID:21420488

    Open questions at the time
    • Whether superoxide itself or a downstream oxidant mediates the Sec-to-DHA conversion is unclear
    • Reversibility of the modification and potential repair mechanisms not explored
  8. 2012 High

    Identifying TFAP2C as a direct transcriptional activator of GPX1 whose binding is abolished by CpG methylation provided a mechanism for epigenetic silencing of GPX1 in cancer.

    Evidence ChIP-seq, TFAP2C knockdown, 5-aza-dC demethylation rescue, GPX activity assay, primary tumor methylation analysis

    PMID:22964634

    Open questions at the time
    • Which DNA methyltransferase(s) deposit the silencing mark at the AP-2 site in vivo not fully established (DNMT2 implicated later in a specific context)
    • Whether TFAP2C is the dominant transcription factor for GPX1 in non-tumor tissues unknown
  9. 2014 Medium

    Showing that mTOR inhibition increases GPX1 protein without changing mRNA identified an additional translational control layer, distinct from SECIS/homocysteine regulation.

    Evidence Rapamycin treatment of CML cells, western blot vs. mRNA quantification

    PMID:24691473

    Open questions at the time
    • Whether mTOR regulates GPX1 translation via 4E-BP/eIF4E, S6K, or through SECIS-binding factors is unresolved
    • Generalizability beyond CML cell lines not tested
  10. 2016 High

    Identification of a CUEDC2–TRIM33 axis that ubiquitinates GPX1 for proteasomal degradation established a targeted proteolytic control mechanism with pathophysiological relevance in cardiac ischemia-reperfusion injury.

    Evidence Cuedc2 knockout mice, Co-IP of CUEDC2–TRIM33–GPX1 complex, ubiquitination assay, ischemia-reperfusion injury model

    PMID:27286733

    Open questions at the time
    • Specific ubiquitinated lysine(s) on GPX1 not mapped
    • Whether TRIM33 is the sole E3 ligase for GPX1 is unknown
  11. 2020 Medium

    Demonstration that PER1 physically interacts with GPX1 and enhances its activity connected the circadian clock to mitochondrial redox oscillations.

    Evidence Reciprocal Co-IP of PER1–GPX1, Per1 knockout mice, GPX activity assay, mitochondrial oxygen consumption measurement

    PMID:32896721

    Open questions at the time
    • Structural basis of PER1–GPX1 interaction unknown
    • Whether the interaction is direct or mediated by a bridging partner not resolved
    • Circadian oscillation of GPX1 activity not measured with temporal resolution
  12. 2022 High

    Discovery that NONO binds GPX1 pre-mRNA intron and promotes correct splicing (with PSPC1) added a splicing-level regulatory layer; NONO loss causes intron retention and functional GPX1 deficiency.

    Evidence RIP-PCR, RNA pulldown, RNA sequencing, NONO knockdown/overexpression, Seahorse assay in glioblastoma cells

    PMID:35910786

    Open questions at the time
    • Sequence specificity of the NONO-binding motif in GPX1 intron not fully defined
    • Whether this splicing regulation operates in non-cancer cell types unknown
  13. 2023 Medium

    Showing that HIF-1α directly binds the GPX1 promoter under hypoxia to induce expression revealed how GPX1 is upregulated in the hypoxic tumor microenvironment; exosomal GPX1 transfer to endothelial cells extended GPX1 function beyond cell-autonomous antioxidant defense.

    Evidence ChIP of HIF-1α at GPX1 promoter, GPX1 knockdown, H2O2 measurement, xenograft model, exosome characterization

    PMID:37572455

    Open questions at the time
    • Relative contribution of HIF-1α vs. TFAP2C to GPX1 transcription under normoxic vs. hypoxic conditions not compared
    • Mechanism of GPX1 sorting into exosomes not elucidated
  14. 2024 High

    Identification of S-palmitoylation at C76 and C113 as a stabilizing modification, reversed by PPT1 depalmitoylase, established a lipid-modification axis controlling GPX1 turnover with functional impact on pathological angiogenesis.

    Evidence Site-directed mutagenesis of C76/C113, PPT1 knockout mice (OIR model), PPT1 inhibitor DC661, protein stability assay

    PMID:39423458

    Open questions at the time
    • Which palmitoyl acyltransferase(s) modify GPX1 is unknown
    • How palmitoylation and O-GlcNAcylation are coordinated on the same protein not explored

Open questions

Synthesis pass · forward-looking unresolved questions
  • A unified structural and kinetic model integrating the multiple post-translational modifications (O-GlcNAcylation, S-palmitoylation, ubiquitination, Sec-to-DHA conversion) and their crosstalk on GPX1 activity and stability remains to be constructed.
  • No high-resolution structure of human GPX1 with mapped PTM sites exists
  • Quantitative hierarchy among transcriptional (TFAP2C, HIF-1α), translational (SECIS, mTOR), splicing (NONO), and post-translational controls not established
  • Cell-type-specific integration of these regulatory layers not systematically characterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016209 antioxidant activity 4 GO:0016491 oxidoreductase activity 3
Localization
GO:0005739 mitochondrion 2 GO:0005829 cytosol 2
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-9909396 Circadian clock 1
Partners
ABL1ARGCUEDC2NONOPER1PPT1PSPC1TRIM33

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 The Gpx1 gene encodes both cytosolic and mitochondrial glutathione peroxidase in mouse liver; mitochondrial GPX activity was completely absent in Gpx1-knockout mice, establishing that mitochondrial GPX is a product of the Gpx1 gene. Subcellular fractionation (Percoll gradient), enzymatic activity assay in Gpx1 knockout vs. wild-type mice Archives of biochemistry and biophysics High 9126277
1998 GPX1 protects cells against oxidative stress caused by paraquat and H2O2; Gpx1-/- mice showed dramatically increased lethality to paraquat and cortical neurons from Gpx1-/- mice were more susceptible to H2O2-induced death. Loss-of-function (Gpx1 knockout mouse), in vivo oxidant challenge (paraquat, H2O2), primary neuron culture The Journal of biological chemistry High 9712879
2001 GPX1 gene delivery (adenoviral GPx-1 overexpression) suppresses H2O2-mediated NF-κB activation preferentially through inhibition of IKKα but not IKKβ, linking GPX1-mediated H2O2 clearance to a specific subunit of the IKK complex. Adenoviral overexpression of GPx-1 and dominant-negative IKKα/IKKβ constructs, NF-κB reporter assay, EMSA Antioxidants & redox signaling Medium 11491654
2004 GPX1 overexpression in MCF-7 cells decreases site-specific Akt phosphorylation, increases Gadd45 levels, and affects p70S6K phosphorylation without affecting ERK1/2 or p38 MAPK, placing GPX1 in the PI3K-Akt survival signaling pathway. Stable transfection (GPx-1 overexpression), western blotting for phosphoprotein levels Free radical biology & medicine Medium 15203190
2004 Fibroblasts from Gpx1-/- mice display senescence-like features including reduced proliferative capacity, elevated Cip1, increased NF-κB activation, and increased susceptibility to H2O2-induced apoptosis, demonstrating that GPX1 protects against ROS-mediated senescence and cell death. Primary fibroblasts from Gpx1 knockout mice, proliferation assays, apoptosis assay, NF-κB reporter Free radical biology & medicine Medium 14732290
2005 Loss of Gpx1 in neurons leads to diminished Akt phosphorylation (PI3K-Akt pathway) following H2O2 treatment and after cerebral ischemia-reperfusion, mechanistically linking GPX1 to neuronal survival via the PI3K-Akt pathway. Primary neurons from Gpx1-/- mice, H2O2 challenge, PI3K inhibitor (LY294002) treatment, western blot for phospho-Akt, MCAO model Journal of neurochemistry Medium 15663476
2005 Homocysteine decreases GPX1 activity by impairing the translational selenocysteine-insertion (UGA read-through) mechanism, without affecting GPX1 mRNA levels; the effect is mediated through the SECIS element in the 3'-UTR of GPX1 mRNA. SECIS-luciferase reporter assay, enzymatic activity assay, western blot, metabolic manipulation of homocysteine using folate antagonist The Journal of biological chemistry High 15734734
2005 GPX1 overexpression in endothelial cells reduces Bax protein and mRNA levels (without changing p53 or Bcl-2), lowering the Bax/Bcl-2 apoptotic ratio in the absence of exogenous oxidant stress. Stable transfection, quantitative RT-PCR, western blot Molecular and cellular biochemistry Low 16132718
2009 GPX1 is modified with O-linked N-acetylglucosamine (O-GlcNAc) on its C-terminus under hyperglycemic conditions; this O-GlcNAcylation is required for GPX1 activation and for GPX1 binding to c-Abl and Arg kinases. Co-immunoprecipitation, O-GlcNAcase inhibitor (NTZ) injection, enzymatic activity assay, glycosylation analysis Biochemical and biophysical research communications Medium 19944066
2011 Knockout of SOD1 promotes conversion of the active-site selenocysteine (Sec) of hepatic GPX1 to dehydroalanine (DHA), reducing apparent kcat and GPX1 activity, revealing in vivo functional dependence of GPX1 on SOD1 through an oxidative active-site modification. Mass spectrometry of GPX1 active-site residue in SOD1-/- mice, in vitro kinetics, tetramer structure analysis Free radical biology & medicine High 21420488
2011 Naked mole rats have drastically reduced GPX1 expression due to an early stop codon in the GPX1 gene and defective SECIS/mRNA function, resulting in reduced selenium utilization in liver and kidney; GPX1 knockout mice similarly show reduced selenium in these tissues, establishing GPX1 as a major selenium-utilizing enzyme. Transcriptome sequencing, heterologous expression in HEK293 cells, 75Se metabolic labeling, x-ray fluorescence microscopy, GPX1 KO mouse analysis The Journal of biological chemistry High 21372135
2012 Transcription factor ZNF143 upregulates GPX1 activity in mitochondrial respiratory-defective cells; ZNF143 knockdown reduces GPX1 activity, and ZNF143 also activates the selenocysteine synthesis pathway (SepSecS expression), promoting cell survival under oxidative stress. ZNF143 and GPX1 knockdown (siRNA), GPX activity assay, gene expression analysis, cisplatin sensitivity assay Cell death & disease Medium 23152058
2012 TFAP2C transcription factor directly binds an AP-2 regulatory element in the GPX1 promoter and activates GPX1 transcription; CpG methylation of this AP-2 site blocks TFAP2C binding and silences GPX1; demethylation with 5-aza-dC restores TFAP2C binding and GPX1 expression. ChIP-seq, TFAP2C knockdown, 5'-aza-dC treatment, GPX activity assay, methylation analysis of primary tumors Oncogene High 22964634
2014 mTOR pathway activity regulates GPX1 (and GPX4) at the translational level; rapamycin (mTOR inhibitor) increases GPX1 protein levels without altering mRNA, indicating mTOR suppresses GPX1 translation. Rapamycin treatment of CML cell lines, western blot, mRNA quantification PloS one Medium 24691473
2016 CUEDC2 promotes TRIM33-mediated ubiquitination and proteasomal degradation of GPX1 in cardiomyocytes; Cuedc2 knockout increases GPX1 protein levels, enhances ROS scavenging, and protects against ischemia/reperfusion injury. Cuedc2 knockout mice, Co-IP (CUEDC2-TRIM33-GPX1 interaction), ubiquitination assay, I/R injury model EMBO molecular medicine High 27286733
2020 PER1 physically interacts with GPX1 in the cytoplasm and enhances GPX1 activity; Per1-deficient mice show deregulated GPX-related ROS fluctuations and impaired mitochondrial oxidative phosphorylation efficiency, placing PER1 as a regulator of GPX1-dependent redox homeostasis. Co-immunoprecipitation (PER1/GPX1), Per1 knockout mice, GPX activity assay, oxygen consumption measurement, mitochondrial function assay Redox biology Medium 32896721
2022 DNMT2-mediated DNA methylation of the GPX1 promoter suppresses GPX1 expression in AGE-exposed cardiomyocytes; selenium supplementation reduces DNMT2 expression, decreases GPX1 promoter methylation, restores GPX1 activity, and alleviates ROS-mediated apoptosis. Bisulfite sequencing, DNMT inhibitor (AZA), selenium supplementation, western blot, GPX activity assay, cardiac function assessment in rats Oxidative medicine and cellular longevity Medium 35432721
2022 The splicing factor NONO binds a consensus motif in the intron of GPX1 pre-mRNA (in association with PSPC1) and promotes correct splicing; NONO knockdown causes GPX1 intron retention, reducing functional GPX1 and impairing redox homeostasis in glioblastoma cells. RIP-PCR, RNA pulldown, RNA sequencing, NONO knockdown/overexpression, JC-1 staining, Seahorse assay Theranostics High 35910786
2023 HIF-1α binds the GPX1 promoter under hypoxic conditions to induce GPX1 expression; GPX1 depletion under hypoxia leads to H2O2 overload and apoptosis in glioblastoma; exosomal GPX1 additionally protects neighboring endothelial cells from H2O2- or radiation-induced apoptosis. ChIP (HIF-1α/GPX1 promoter), GPX1 knockdown, H2O2 measurement, xenograft model, exosome characterization Redox biology Medium 37572455
2024 GPX1 undergoes S-palmitoylation at cysteine-76 and cysteine-113; the depalmitoylase PPT1 promotes GPX1 depalmitoylation and reduces GPX1 protein stability. Inhibiting palmitoylation (or expressing PPT1) enhances angiogenesis, while PPT1 deficiency attenuates pathological angiogenesis, establishing a PPT1-GPX1 palmitoylation axis regulating angiogenesis. Site-directed mutagenesis (C76/C113 non-palmitoylatable mutants), PPT1 knockout mice (OIR model), PPT1 inhibitor (DC661), protein stability assay 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 353 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 263 28089078
2004 Bacteria-induced intestinal cancer in mice with disrupted Gpx1 and Gpx2 genes. Cancer research 239 14871826
2001 Mice with combined disruption of Gpx1 and Gpx2 genes have colitis. American journal of physiology. Gastrointestinal and liver physiology 233 11518697
2005 Associations between GPX1 Pro198Leu polymorphism, erythrocyte GPX activity, alcohol consumption and breast cancer risk in a prospective cohort study. Carcinogenesis 178 16287877
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 104 20828612
2005 Homocysteine down-regulates cellular glutathione peroxidase (GPx1) by decreasing translation. The Journal of biological chemistry 104 15734734
2010 Antiatherosclerotic and renoprotective effects of ebselen in the diabetic apolipoprotein E/GPx1-double knockout mouse. Diabetes 99 20823099
2008 Sensitization by docosahexaenoic acid (DHA) of breast cancer cells to anthracyclines through loss of glutathione peroxidase (GPx1) response. Free radical biology & medicine 93 18267129
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
2010 Knockouts of SOD1 and GPX1 exert different impacts on murine islet function and pancreatic integrity. Antioxidants & redox signaling 76 20586612
2001 GPx-1 gene delivery modulates NFkappaB activation following diverse environmental injuries through a specific subunit of the IKK complex. Antioxidants & redox signaling 76 11491654
2022 Glutathione Peroxidase GPX1 and Its Dichotomous Roles in Cancer. Cancers 75 35626163
2009 Association between GPx1 Pro198Leu polymorphism, GPx1 activity and plasma selenium concentration in humans. European journal of nutrition 75 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
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
2006 Gene x Gene interaction between MnSOD and GPX-1 and breast cancer risk: a nested case-control study. BMC cancer 65 16945136
2015 MicroRNA-153/Nrf-2/GPx1 pathway regulates radiosensitivity and stemness of glioma stem cells via reactive oxygen species. Oncotarget 64 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
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
2018 A possible role for selenoprotein glutathione peroxidase (GPx1) and thioredoxin reductases (TrxR1) in thyroid cancer: our experience in thyroid surgery. Cancer cell international 53 29371830
2014 X-Ray fluorescence imaging and other analyses identify selenium and GPX1 as important in female reproductive function. Metallomics : integrated biometal science 52 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 47 35910786
2005 Diminished Akt phosphorylation in neurons lacking glutathione peroxidase-1 (Gpx1) leads to increased susceptibility to oxidative stress-induced cell death. Journal of neurochemistry 47 15663476
2012 Transcriptional regulation of the GPX1 gene by TFAP2C and aberrant CpG methylation in human breast cancer. Oncogene 46 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
2013 Lack of the antioxidant glutathione peroxidase-1 (GPx1) exacerbates retinopathy of prematurity in mice. Investigative ophthalmology & visual science 43 23287791
2020 PER1 interaction with GPX1 regulates metabolic homeostasis under oxidative stress. Redox biology 41 32896721
2013 Protective effects of total flavonoids from Epimedium on the male mouse reproductive system against cyclophosphamide-induced oxidative injury by up-regulating the expressions of SOD3 and GPX1. Phytotherapy research : PTR 41 23494828
2021 CCL5 via GPX1 activation protects hippocampal memory function after mild traumatic brain injury. Redox biology 40 34315111
2012 Selenium blocks porcine circovirus type 2 replication promotion induced by oxidative stress by improving GPx1 expression. Free radical biology & medicine 38 22580339
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
2015 Glutathione peroxidase-1 gene (GPX1) variants, oxidative stress and risk of kidney complications in people with type 1 diabetes. Metabolism: clinical and experimental 35 26773925
2010 Frequency of polymorphisms pro198leu in GPX-1 gene and ile58thr in MnSOD gene in the altitude Ecuadorian population with bladder cancer. Oncology research 35 20441054
2008 The effects of GPX-1 knockout on membrane transport and intracellular homeostasis in the lens. The Journal of membrane biology 35 19067024
2016 Deficiency in Duox2 activity alleviates ileitis in GPx1- and GPx2-knockout mice without affecting apoptosis incidence in the crypt epithelium. Redox biology 34 27930931
2004 Allelic loss at the GPx-1 locus in cancer of the head and neck. Biological trace element research 32 15557674
2002 Association between the GCG polymorphism of the selenium dependent GPX1 gene and the risk of young onset prostate cancer. Prostate cancer and prostatic diseases 32 12496980
2023 Cellular and exosomal GPx1 are essential for controlling hydrogen peroxide balance and alleviating oxidative stress in hypoxic glioblastoma. Redox biology 31 37572455
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
2004 GPx-1 modulates Akt and P70S6K phosphorylation and Gadd45 levels in MCF-7 cells. Free radical biology & medicine 31 15203190
2022 Selenium Supplementation Improved Cardiac Functions by Suppressing DNMT2-Mediated GPX1 Promoter DNA Methylation in AGE-Induced Heart Failure. Oxidative medicine and cellular longevity 30 35432721
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
2013 p53 mutations may be involved in malignant transformation of giant cell tumor of bone through interaction with GPX1. Virchows Archiv : an international journal of pathology 30 23748877
2013 The modified selenenyl amide, M-hydroxy ebselen, attenuates diabetic nephropathy and diabetes-associated atherosclerosis in ApoE/GPx1 double knockout mice. PloS one 29 23874911
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
2018 Evaluation of the oxidative stress-related genes ALOX5, ALOX5AP, GPX1, GPX3 and MPO for contribution to the risk of type 2 diabetes mellitus in the Han Chinese population. Diabetes & vascular disease research 28 29383971
2012 ZNF143 transcription factor mediates cell survival through upregulation of the GPX1 activity in the mitochondrial respiratory dysfunction. Cell death & disease 28 23152058
2011 Association of GPX1 polymorphism, GPX activity and prostate cancer risk. Human & experimental toxicology 28 21636625
2023 Selenium deficiency causes hypertension by increasing renal AT1 receptor expression via GPx1/H2O2/NF-κB pathway. Free radical biology & medicine 27 36868433
2011 Reduced utilization of selenium by naked mole rats due to a specific defect in GPx1 expression. The Journal of biological chemistry 25 21372135
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
2006 Genetic association analysis of the glutathione peroxidase (GPX1) gene polymorphism (Pro197Leu) with tardive dyskinesia. Psychiatry research 25 16413612
2016 1,25-Dihydroxyvitamin D3 alleviates salivary adenoid cystic carcinoma progression by suppressing GPX1 expression through the NF-κB pathway. International journal of oncology 24 26782341
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
2003 Overexpression of cytosolic glutathione peroxidase (GPX1) delays endothelial cell growth and increases resistance to toxic challenges. Biochimie 24 12829378
2023 Selenium-modified bone cement promotes osteoporotic bone defect repair in ovariectomized rats by restoring GPx1-mediated mitochondrial antioxidant functions. Regenerative biomaterials 23 36852397
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
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 22 35597264
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
2024 Selenium nanoparticles ameliorate lumbar disc degeneration by restoring GPX1-mediated redox homeostasis and mitochondrial function of nucleus pulposus cells. Journal of nanobiotechnology 21 39420311
2014 Association of glutathione peroxidase-1 (GPx-1) rs1050450 Pro198Leu and Pro197Leu polymorphisms with cardiovascular risk: a meta-analysis of observational studies. Journal of geriatric cardiology : JGC 21 25009565
2009 Selenium requirements are higher for glutathione peroxidase-1 mRNA than gpx1 activity in rat testis. Experimental biology and medicine (Maywood, N.J.) 20 19234057
2024 Polystyrene microplastics trigger testosterone decline via GPX1. The Science of the total environment 19 38977086
2014 Translational regulation of GPx-1 and GPx-4 by the mTOR pathway. PloS one 19 24691473
2011 Knockout of SOD1 promotes conversion of selenocysteine to dehydroalanine in murine hepatic GPX1 protein. Free radical biology & medicine 19 21420488
2016 Directed Differentiation of Dopamine-Secreting Cells from Nurr1/GPX1 Expressing Murine Embryonic Stem Cells Cultured on Matrigel-Coated PCL Scaffolds. Molecular neurobiology 18 26803497
2013 The effects of selenium and the GPx-1 selenoprotein on the phosphorylation of H2AX. Biochimica et biophysica acta 18 23518201
2012 Association between polymorphisms of eNOS and GPx-1 genes, activity of free-radical processes and in-stent restenosis. Molecular and cellular biochemistry 18 22890915
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
2021 Crocin Improves Endothelial Mitochondrial Dysfunction via GPx1/ROS/KCa3.1 Signal Axis in Diabetes. Frontiers in cell and developmental biology 17 33777959
2010 Lipopolysaccharide-induced hepatic oxidative injury is not potentiated by knockout of GPX1 and SOD1 in mice. Biochemical and biophysical research communications 17 21145306
2024 Enhancing Gpx1 palmitoylation to inhibit angiogenesis by targeting PPT1. Redox biology 16 39423458
2022 Glutathione Regulates GPx1 Expression during CA1 Neuronal Death and Clasmatodendrosis in the Rat Hippocampus following Status Epilepticus. Antioxidants (Basel, Switzerland) 16 35453441
2017 The role of GPX1 in the pathogenesis of female pelvic organ prolapse. PloS one 16 28783735
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
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
1994 An in-frame trinucleotide repeat in the coding region of the human cellular glutathione peroxidase (GPX1) gene: in vivo polymorphism and in vitro instability. Genomics 16 7829093
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) 15 36295574
2018 Sodium selenite inhibits deoxynivalenol-induced injury in GPX1-knockdown porcine splenic lymphocytes in culture. Scientific reports 15 30518949
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
2023 Selenium-ruthenium complex blocks H1N1 influenza virus-induced cell damage by activating GPx1/TrxR1. Theranostics 14 37064873
2021 Genetic variations of three important antioxidative enzymes SOD2, CAT, and GPX1 in nonalcoholic steatohepatitis. Journal of the Chinese Medical Association : JCMA 14 33009206
2024 Translational selenium nanoparticles boost GPx1 activation to reverse HAdV-14 virus-induced oxidative damage. Bioactive materials 13 38745588
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