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Tetsuro Okamoto - One of the best experts on this subject based on the ideXlab platform.
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Glutathione s transferase p1 1 protects aberrant crypt foci from apoptosis induced by deoxycholic acid
Gastroenterology, 2004Co-Authors: Atsushi Nobuoka, Tetsuji Takayama, Koji Miyanishi, Takehiro Kukitsu, Kunihiro Takanashi, Tsuyoshi Hayashi, Tsutomu Sato, Minoru Takahashi, Yasushi Sato, Tetsuro OkamotoAbstract:Abstract Background & Aims: Aberrant crypt foci, precursors of colonic adenoma, are frequently positive for Glutathione- S -transferase P1-1. Because deoxycholic acid is an apoptosis-inducing xenobiotic in the colon, we examined the possibility that aberrant crypt foci, through the cytoprotecting function of Glutathione- S -transferase P1-1, resist deoxycholic acid-induced apoptosis, thereby surviving to become adenomas and subsequently cancer. Methods: Glutathione- S -transferase P1-1 or cyclooxygenase-2 expression and the percentage of apoptotic cells in aberrant crypt foci were examined by immunohistochemistry and by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling, respectively. Glutathione-S-Transferase P1-1 was transfected into colon cancer cells (M7609) and human lung fibroblasts, and deoxycholic acid-induced apoptosis was evaluated by a dye-uptake assay and flow cytometry. Binding of deoxycholic acid to Glutathione- S -transferase P1-1 was analyzed by circular dichroism and immunoprecipitation. Caspase activities were determined by colorimetric protease assay, and sulindac binding to Glutathione- S -transferase P1-1 was determined by inhibition assay of Glutathione- S -transferase P1-1 activity. Results: Aberrant crypt foci showed positive immunostaining for Glutathione- S -transferase P1-1 but negative staining for cyclooxygenase-2. The percentage of apoptotic cells in aberrant crypt foci was significantly lower than in healthy epithelium, and the difference became more apparent with deoxycholic acid treatment. The impaired sensitivity of aberrant crypt foci to deoxycholic acid was restored by the Glutathione- S -transferase P1-1-specific inhibitor γ-glutamyl- S -(benzyl)cysteinyl- R -phenylglycine diethylester. By transfection of Glutathione-S-Transferase P1-1 , M7609 cells became more resistant to deoxycholic acid-induced apoptosis than mock transfectants. Direct binding of Glutathione- S -transferase P1-1 to deoxycholic acid was proven by circular dichroism and by immunoprecipitation. The aberrant crypt foci in adenoma patients treated with sulindac, which was shown to bind to Glutathione- S -transferase P1-1, underwent apoptosis in 4 days and mostly regressed in 2–3 months. Conclusions: Glutathione- S -transferase P1-1 protects aberrant crypt foci from deoxycholic acid-induced apoptosis and may play a pivotal role in early colon carcinogenesis.
Xiaohui Xu - One of the best experts on this subject based on the ideXlab platform.
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Glutathione s transferase m1 gstm1 and Glutathione s transferase t1 gstt1 null polymorphisms smoking and their interaction in oral cancer a huge review and meta analysis
American Journal of Epidemiology, 2011Co-Authors: Zhijiang Zhang, Genming Zhao, Guo Xin Jiang, Yiqing Song, Xiaohui XuAbstract:The association between Glutathione S-Transferase M1 (GSTM1) and Glutathione S-Transferase T1 (GSTT1) null polymorphisms and oral cancer is not consistent across studies, and data on their interaction with smoking in oral cancer are lacking. The authors systematically searched PubMed and SciVerse Scopus for case-control studies examining the association between null genotypes of the GSTM1 and GSTT1 genes and oral cancer. Twenty-eight case-control studies published in English were identified. Summary odds ratios were derived via random-effects models. The summary odds ratio for the GSTM1 null genotype was 1.43 in Asians (95% confidence interval (CI): 1.14, 1.78; P < 0.01, I 2 ¼ 73%) and 0.98 in Caucasians (95% CI: 0.76, 1.28; P ¼ 0.91, I 2 ¼ 0%). Case-only analysis of 6 studies (552 cases) showed an inverse multiplicative interaction between GSTM1 null polymorphisms and smoking (ever/high levels of smoking vs. never/low levels) (odds ratio (OR) ¼ 0.51, 95% CI: 0.32, 0.82; P ¼ 0.01, I 2 ¼ 34%). The GSTT1 null genotype was not significantly associated with oral cancer in Asians (OR ¼ 1.07, 95% CI: 0.82, 1.38; P ¼ 0.63, I 2 ¼ 65%) or Caucasians (OR ¼ 1.04, 95% CI: 0.41, 2.65; P ¼ 0.93, I 2 ¼ 55%). In conclusion, the GSTM1 null genotype may be associated with a higher risk of oral cancer in Asians but not in Caucasians, and this effect may be modified by smoking status. The GSTT1 null genotype may not be associated with oral cancer. case-control studies; genome, human; Glutathione transferase; interaction; meta-analysis; mouth neoplasms; polymorphism, genetic; polymorphism, single nucleotide
Yogesh C. Awasthi - One of the best experts on this subject based on the ideXlab platform.
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naturally occurring human Glutathione s transferase gstp1 1 isoforms with isoleucine and valine in position 104 differ in enzymic properties
FEBS Journal, 1994Co-Authors: Piotr Zimniak, Bindu Nanduri, Slawomir Pikula, Joanna Bandorowiczpikula, Sharad S Singhal, Sanjay Srivastava, Sanjay Awasthi, Yogesh C. AwasthiAbstract:Glutathione S-Transferase P1-1 isoforms, differing in a single amino acid residue (Ile104 or Val104), have been previously identified in human placenta [Ahmad, H., Wilson, D. E., Fritz, R. R., Singh, S. V., Medh, R. D., Nagle, G. T., Awasthi, Y. C. & Kurosky, A. (1990) Arch. Biochem. Biophys. 278, 398–408]. In the present report, the enzymic properties of these two proteins are compared. [I104]Glutathione S-Transferase P1-1 has been expressed from its cDNA in Escherichia coli and purified to homogeneity by affinity chromatography; the cDNA has been mutated to replace Ile104 by Val104, and [V104]Glutathione S-Transferase P1-1 was expressed and isolated as described for [I104]Glutathione S-Transferase P1-1. The two enzymes differed in their specific activity and affinity for electrophilic substrates (KM values for 1-chloro-2,4-dinitrobenzene were 0.8 mM and 3.0 mM for [I-104]Glutathione S-Transferase P1-1 and [V-104]Glutathione S-Transferase P1-1, respectively), but were identical in their affinity for Glutathione. In addition, the two enzymes were distinguishable by their heat stability, with half-lives at 45°C of 19 min and 51 min, respectively. The resistance to heat denaturation was differentially modulated by the presence of substrates. These data, in conjunction with molecular modeling, indicate that the residue in position 104 helps to define the geometry of the hydrophobic substrate-binding site, and may also influence activity by interacting with residues directly involved in substrate binding.
Atsushi Nobuoka - One of the best experts on this subject based on the ideXlab platform.
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Glutathione s transferase p1 1 protects aberrant crypt foci from apoptosis induced by deoxycholic acid
Gastroenterology, 2004Co-Authors: Atsushi Nobuoka, Tetsuji Takayama, Koji Miyanishi, Takehiro Kukitsu, Kunihiro Takanashi, Tsuyoshi Hayashi, Tsutomu Sato, Minoru Takahashi, Yasushi Sato, Tetsuro OkamotoAbstract:Abstract Background & Aims: Aberrant crypt foci, precursors of colonic adenoma, are frequently positive for Glutathione- S -transferase P1-1. Because deoxycholic acid is an apoptosis-inducing xenobiotic in the colon, we examined the possibility that aberrant crypt foci, through the cytoprotecting function of Glutathione- S -transferase P1-1, resist deoxycholic acid-induced apoptosis, thereby surviving to become adenomas and subsequently cancer. Methods: Glutathione- S -transferase P1-1 or cyclooxygenase-2 expression and the percentage of apoptotic cells in aberrant crypt foci were examined by immunohistochemistry and by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling, respectively. Glutathione-S-Transferase P1-1 was transfected into colon cancer cells (M7609) and human lung fibroblasts, and deoxycholic acid-induced apoptosis was evaluated by a dye-uptake assay and flow cytometry. Binding of deoxycholic acid to Glutathione- S -transferase P1-1 was analyzed by circular dichroism and immunoprecipitation. Caspase activities were determined by colorimetric protease assay, and sulindac binding to Glutathione- S -transferase P1-1 was determined by inhibition assay of Glutathione- S -transferase P1-1 activity. Results: Aberrant crypt foci showed positive immunostaining for Glutathione- S -transferase P1-1 but negative staining for cyclooxygenase-2. The percentage of apoptotic cells in aberrant crypt foci was significantly lower than in healthy epithelium, and the difference became more apparent with deoxycholic acid treatment. The impaired sensitivity of aberrant crypt foci to deoxycholic acid was restored by the Glutathione- S -transferase P1-1-specific inhibitor γ-glutamyl- S -(benzyl)cysteinyl- R -phenylglycine diethylester. By transfection of Glutathione-S-Transferase P1-1 , M7609 cells became more resistant to deoxycholic acid-induced apoptosis than mock transfectants. Direct binding of Glutathione- S -transferase P1-1 to deoxycholic acid was proven by circular dichroism and by immunoprecipitation. The aberrant crypt foci in adenoma patients treated with sulindac, which was shown to bind to Glutathione- S -transferase P1-1, underwent apoptosis in 4 days and mostly regressed in 2–3 months. Conclusions: Glutathione- S -transferase P1-1 protects aberrant crypt foci from deoxycholic acid-induced apoptosis and may play a pivotal role in early colon carcinogenesis.
Mostafa Saadat - One of the best experts on this subject based on the ideXlab platform.
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genetic polymorphisms of Glutathione s transferase t1 gstt1 and susceptibility to gastric cancer a meta analysis
Cancer Science, 2006Co-Authors: Mostafa SaadatAbstract:The association between Glutathione S-Transferase T1 (GSTT1) polymorphism and gastric cancer risk has been both confirmed and refuted in a number of published studies. Most of these studies were based on small sample sizes. We carried out a meta-analysis of the research published up to August 2005 to obtain more precise estimates of gastric cancer risk associated with GSTT1 polymorphism. In the present study, 16 case-control studies (with a total of 6717 subjects) were eligible for meta-analysis. There was no evidence of heterogeneity between the studies. The GSTT1 null genotype conferred a 1.06-fold increased risk of gastric cancer, which was not significant (95% confidence interval [CI]: 0.94–1.19). However, in the analysis of ethnic groups, we observed distinct differences associated with GSTT1 status. Restricting analyses to ethnic groups, the pooled odd ratios for the GSTT1 genotype were 1.27 in Caucasians (95% CI: 1.03–1.57) and 0.98 in Asians (95% CI: 0.86–1.13). Glutathione S-Transferase M1 (GSTM1) and GSTT1 are involved in detoxification of a variety of compounds, some that overlap between enzymes and some that are highly specific. To investigate whether the profile of Glutathione S-Transferase genotypes was associated with risk of gastric cancer, further analyses combining the GSTT1 and GSTM1 genotypes were also carried out. There was a significant trend in risk associated with zero, one and two putative high-risk genotypes (χ2 = 9.326, d.f. = 1, P = 0.0023). Those who had null genotypes of GSTM1 and GSTT1 had an increased gastric cancer risk compared with those who had both active genes (odds ratio = 2.08, 95% CI: 1.42–3.10). (Cancer Sci 2006; 97: 505–509)