Human glutathione S-transferase P1-1 functions as an estrogen receptor α signaling modulator

Liu, Xiyuan; An, Byoung Ha; Kim, Min Jung; Park, Jong Hoon; Kang, Young Sook; Chang, Min-Sun

doi:10.1016/j.bbrc.2014.09.017

Cited by 14 publications

(10 citation statements)

References 23 publications

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“…For example, GSTP regulates JNK signaling (Adler et al 1999;Sau et al 2012) and controls the S-glutathionylation of a range of proteins (Townsend et al 2009;Tew et al 2011). GSTP also regulates estrogen response element (ERE)-dependent estrogen receptor alpha (ERa) signaling events (Liu et al 2014b) and is an inhibitor of TRAF2 (De Luca et al 2014).…”

Section: Tissue and Species Distributionmentioning

confidence: 99%

The mercapturic acid pathway

Hanna

Anders

2019

Critical Reviews in Toxicology

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The mercapturic acid pathway is a major route for the biotransformation of xenobiotic and endobiotic electrophilic compounds and their metabolites. Mercapturic acids (N-acetyl-L-cysteine S-conjugates) are formed by the sequential action of the glutathione transferases, c-glutamyltransferases, dipeptidases, and cysteine S-conjugate N-acetyltransferase to yield glutathione S-conjugates, L-cysteinylglycine S-conjugates, L-cysteine S-conjugates, and mercapturic acids; these metabolites constitute a "mercapturomic" profile. Aminoacylases catalyze the hydrolysis of mercapturic acids to form cysteine S-conjugates. Several renal transport systems facilitate the urinary elimination of mercapturic acids; urinary mercapturic acids may serve as biomarkers for exposure to chemicals. Although mercapturic acid formation and elimination is a detoxication reaction, L-cysteine S-conjugates may undergo bioactivation by cysteine Sconjugate b-lyase. Moreover, some L-cysteine S-conjugates, particularly L-cysteinyl-leukotrienes, exert significant pathophysiological effects. Finally, some enzymes of the mercapturic acid pathway are described as the so-called "moonlighting proteins," catalytic proteins that exert multiple biochemical or biophysical functions apart from catalysis.

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Section: Tissue and Species Distributionmentioning

confidence: 99%

The mercapturic acid pathway

Hanna

Anders

2019

Critical Reviews in Toxicology

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“… 10 The GSTP1 gene, located on chromosome 11q13, belongs to the π gene family. 11 The GSTP1 Ile105Val (rs1695 A>G) polymorphism may cause a substitution of isoleucine for valine at codon 105 in the protein, leading to substantial reduction in GSTP1 enzyme activity and its capability of detoxification of carcinogens. 12 …”

Section: Introductionmentioning

confidence: 99%

Association between GSTP1 Ile105Val polymorphism and urinary system cancer risk: evidence from 51 studies

Zhang¹,

Yuan²,

Chen³

et al. 2016

OTT

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The GSTP1 gene plays an important role in detoxification of carcinogens. GSTP1 gene polymorphisms may alter the susceptibility of urinary system cancer. Numerous studies have been performed to investigate the association between GSTP1 Ile105Val (rs1695 A>G) polymorphism and urinary system cancer risk. Nevertheless, the results remain controversial and only prostate cancer and bladder cancer are covered. We identified eligible studies from PubMed, Elsevier, and three equivalent Chinese databases including the Chinese National Knowledge Infrastructure, Wanfang, and Weipu. Pooled odds ratios and 95% confidence intervals were used to assess the strength of the association between GSTP1 Ile105Val polymorphism and urinary system cancer risk. In total, 11,762 cases and 15,150 controls from 51 studies were included in the final meta-analysis. The pooled results from all included studies showed a statistically significant association between GSTP1 Ile105Val polymorphism and urinary system cancer. In the subgroup analyses, the GSTP1 Ile105Val polymorphism was found to be significantly associated with prostate cancer risk and also a risk factor for urinary system cancer among Asians. In conclusion, our meta-analysis indicated that GSTP1 Ile105Val polymorphism was associated with urinary system cancer susceptibility, which needs to be validated by more rigorous data from further large-scale population studies with different ethnicities.

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“…Indeed, our finding that the direct inhibition of 2-Cys PRDX with conoidin A and the specific inhibition of GSTP1, enzyme necessary for the re-activation of PRDX6 peroxidase activity, with ezatiostat [28][29][30][31] induce rapid and extensive cell death in PND3 gonocytes implies that high levels of ROS are formed in these cells in physiological conditions. This further suggests that PRDXs play an essential role in maintaining ROS at levels required for physiological functions, but not high enough to induce cell damage.…”

Section: Discussionmentioning

confidence: 96%

Protective Role of Peroxiredoxins against Reactive Oxygen Species in Neonatal Rat Testicular Gonocytes

et al. 2019

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Peroxiredoxins (PRDXs) are antioxidant enzymes that protect cells from oxidative stress and play a role in reactive oxygen species (ROS)-mediated signaling. We reported that PRDXs are critical for human fertility by maintaining sperm viability and regulating ROS levels during capacitation. Moreover, studies on Prdx6 −/− mice revealed the essential role of PRDX6 in the viability, motility, and fertility competence of spermatozoa. Although PRDXs are abundant in the testis and spermatozoa, their potential role at different phases of spermatogenesis and in perinatal germ cells is unknown. Here, we examined the expression and role of PRDXs in isolated rat neonatal gonocytes, the precursors of spermatogonia, including spermatogonial stem cells. Gene array, qPCR analyses showed that PRDX1, 2, 3, 5, and 6 transcripts are among the most abundant antioxidant genes in postnatal day (PND) 3 gonocytes, while immunofluorescence confirmed the expression of PRDX1, 2, and 6 proteins. The role of PRDXs in gonocyte viability was examined using PRDX inhibitors, revealing that the 2-Cys PRDXs and PRDX6 peroxidases activities are critical for gonocytes viability in basal condition, likely preventing an excessive accumulation of endogenous ROS in the cells. In contrast to its crucial role in spermatozoa, PRDX6 independent phospholipase A 2 (iPLA 2 ) activity was not critical in gonocytes in basal conditions. However, under conditions of H 2 O 2 -induced oxidative stress, all these enzymatic activities were critical to maintain gonocyte viability. The inhibition of PRDXs promoted a two-fold increase in lipid peroxidation and prevented gonocyte differentiation. These results suggest that ROS are produced in neonatal gonocytes, where they are maintained by PRDXs at levels that are non-toxic and permissive for cell differentiation. These findings show that PRDXs play a major role in the antioxidant machinery of gonocytes, to maintain cell viability and allow for differentiation.PRDXs are classified depending on the cysteine residues (Cys) in their active site, that will react with peroxides. They comprise the 2-Cys PRDX1 to 4, the atypical 2-Cys PRDX5, and the 1-Cys PRDX6, which has the particularity of being bifunctional, with both peroxidase and calcium-independent phospholipase A 2 (iPLA 2 ) activities [4]. The 2-Cys PRDX1 to 4 are homodimers in which the thiol of a cysteine residue of one PRDX subunit gets oxidized, then further reacts with the thiol group of the catalytic cysteine of the other subunit, forming a disulfide bond between the two subunits. By contrast, in the atypical PRDX5, 2 Cys of the same chain react upon oxidation to form an intrasubunit disulfide bond. Inactive PRDXs are then reactivated by a reduction of the disulfide bonds by thioredoxin (TRX), itself further reactivated by TRX reductase (TRD), using NADPH as a reducing equivalent. In the case of PRDX6, since the enzyme has only one catalytic Cys, the oxidized thiol will be reduced by the glutathione-GSH-transferase P1 (GSTP1) system [4][5][6].Studies in PRDXs kno...

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Human glutathione S-transferase P1-1 functions as an estrogen receptor α signaling modulator

Cited by 14 publications

References 23 publications

The mercapturic acid pathway

The mercapturic acid pathway

Association between GSTP1 Ile105Val polymorphism and urinary system cancer risk: evidence from 51 studies

Protective Role of Peroxiredoxins against Reactive Oxygen Species in Neonatal Rat Testicular Gonocytes

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