石棉作业对工人血浆中谷胱甘肽S转移酶活性的影响

目的　探讨接触石棉是否会影响工人体内的谷胱甘肽S转移酶 (GST)活性及GSTM1基因型对体内GST活性的影响。方法　选择 94名石棉作业工人及 5 1名对照工人作为研究对象 ,通过问卷调查收集每人的一般情况和职业史等。采集静脉血分离血浆和淋巴细胞 ,血浆用于GST活性测定 ,淋巴细胞用于提取DNA进行GSTM1基因型分析。结果　石棉作业工人血浆中的GST活性 (2 3 0± 6 9)U/L ,明显低于对照组工人的 (32 6± 11 8)U/L ,且随着石棉作业工龄的延长及累积石棉接触剂量的增加 ,工人血浆中的GST活性呈逐渐下降的趋势。用GSTM1基因型对两组工人进行分层后发现 ,携带GSTM1+/ +和GSTM1- / -基因型的石棉作业工人 ,其血浆中的GST活性分别为 (2 4 0±6 1)U/L和 (2 2 5± 7 3)U/L ,均低于同种基因型的对照组工人 ,对照组分别为 (38 1± 13 2 )U/L和(2 6 8± 6 6 )U/L。同时还发现 ,携带GSTM1- / -的对照组工人血浆中的GST活性明显低于携带GSTM1+/ +者 ,而石棉作业工人组虽也有类似趋势 ,但差异无统计学意义。结论　接触石棉可明显降低体内GST的活性。在对照人群中 ,GST活性受GSTM1基因型的影响 ,而在石棉作业工人中 ,这种影响不明显。     

Roles of dietary corn oil in the regulation of cytochromes P450 and glutathione S-transferases in rat liver

To study the molecular mechanisms by which dietary lipids affect the levels of cytochrome P450 (P450) isozymes, male Sprague-Dawley rats were fed either fat-free (FF) or 20% corn oil (CO) diet in combination with one of the following three treatments: no inducer, phenobarbital (PB) and acetone. Dietary CO did not affect the constitutive level of P450IIB (PB-inducible), but it affected the induction of P450IIB by PB treatment. The induction of P450IIB by PB in the CO group as determined by 7-pentoxy-resorufin O-dealkylase activity and immunochemically detected protein level was twofold higher than that in the FF group, and this difference was also reflected in the level of mRNA for this enzyme. In contrast, dietary CO increased the constitutive level of P450IIE (ethanol-inducible) twofold as indicated by N-nitrosodimethylamine demethylase activity and immunochemically detectable protein, but it had no effect on the induction of P450IIE by acetone. The induced level of P450IIE by acetone in the CO group did not differ from that in the FF group as measured by the enzyme activity and protein level. It was demonstrated that dietary CO affects P450IIB and IIE activities by altering the concentration of the isozymes rather than by modulating their catalytic activities. In addition, dietary CO increased the microsomal testosterone 6 beta-hydroxylase activity but not 7 alpha- and 2 alpha-hydroxylase activities, suggesting an increase in P450IIIA and/or IIC13 but not in IIA1 and IIC11, respectively. Dietary CO also affected the constitutive and induced levels of glutathione S-transferase (GST) isozymes in a different manner: it increased the constitutive level of GST-B but not that of GST-A. Nevertheless, it was important for the induction of both GST-A and GST-B by PB treatment. The results suggest that lipid nutrition affects xenobiotic metabolism activities by altering constitutive and inducible levels of certain P450 and GST isozymes.     

Effect of ethanol on lipid composition of neonatal chick liver

The effects of short-term (60 h) and long-term (18 days) ethanol treatment on different liver parameters have been studied in neonatal chicks. Long-term ethanol exposure significantly decreased liver weight, while body and brain weights were less affected. Both short and long-term treatments induced a clear decrease in hepatic alcohol dehydrogenase activity. Ethanol feeding did not induce alterations in plasma and liver triglyceride concentrations. Likewise, 60 h ethanol administration did not alter hepatic cholesterol content, while a 18 days treatment induced a clear decrease in total cholesterol content, mainly due to a reduction in free cholesterol. Practically no effect of ethanol was observed on the phospholipid content after both short and long-term treatments. However, marked modifications in the hepatic fatty acid distribution were found in both cases, although the double bond index and unsaturated to saturated fatty acids ratio were clearly increased only after 18 days ethanol administration.     

Green tea consumption and glutathione S-transferases genetic polymorphisms on the risk of adult leukemia

Purpose

Green tea may have a beneficial role of inhibiting leukemia. Glutathione S-transferases (GSTs) are known to detoxify certain carcinogens. We investigated the roles of green tea consumption and polymorphisms of GSTM1, GSTT1 and GSTP1 on the risk of adult leukemia, and to determine whether the associations varied within GSTs genotypes.

Methods

A multicenter case–control study was conducted in China, 2008–2013. It comprised 442 incident, hematologically confirmed adult leukemia cases and 442 outpatient controls, individually matched to cases by gender, birth quinquennium and study site. Data were collected by face-to-face interview using a validated questionnaire. Genetic polymorphisms were assayed by PCR.

Results

An inverse association between green tea consumption and adult leukemia risk was observed. Compared with non-tea drinkers, the adjusted odds ratios (95 % confidence intervals) were 0.50 (0.27–0.93), 0.31 (0.17–0.55) and 0.53 (0.29–0.99) for those who, respectively, consumed green tea >20 years, ≥2 cups daily and dried tea leaves >1000 g annually. In assessing the associations by GSTs genotypes, risk reduction associated with green tea consumption was stronger in individuals with the GSTT1-null genotype (OR 0.24; 95 % CI 0.11–0.53) than GSTT1-normal carriers (OR 0.67; 95 % CI 0.42–1.05; P interaction = 0.02). GSTM1 and GSTP1 did not significantly modify the inverse association of leukemia with green tea.

Conclusions

The results suggest that regular daily green tea consumption may reduce leukemia risk in Chinese adults regardless of GSTM1 and GSTP1 polymorphic status. The association between green tea and adult leukemia risk varied with GSTT1 genotype and highlights further study.

     

Characterization of cytosolic glutathione S-transferases in striped bass (Morone saxitilis)

Electrophilic compounds are ubiquitous in the environment and aquatic life is inevitably affected. Glutathione S-transferases (GSTs) are a class of enzymes that facilitate the detoxification of these electrophiles in phase II metabolism. In this study, cytosolic GSTs were isolated and characterized from striped bass liver (Morone saxitilis). Nanospray liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to elucidate peptide sequences, and the proteins were found to have homology to rho and alpha by searching against the NCBI non-redundant database (nrDB). Catalytic activities of the cytosolic GSTs towards 1-chloro-2,4-dinitrobenzene (CDNB) were determined to be 141+/-34 and 155+/-65nmol/min/mg for males and females, respectively (both n=3). However, sex differences in classes expressed and activity toward CDNB were not statistically significant (p>0.05).     

Characterization of cytosolic glutathione S-transferases in California Halibut (Paralichthys californicus)

Two cytosolic glutathione S-transferase (GST) classes were isolated and characterized from California halibut (Paralichthys californicus) liver. Nanospray liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to elucidate peptide sequences and the proteins were identified as theta and alpha by searching against the NCBI non-redundant database (nrDB). Catalytic activity of the cytosolic GSTs towards 1-chloro-2,4-dinitrobenzene (CDNB) was determined to be 0.23+/-0.003 U/mg cytosolic protein.     

Effect of methylmercury on the activity of glutathione peroxidase in rat liver

The effect of methylmercury on the activity of glutathione peroxidase in rat liver was studied in vivo. A daily dose of 10mg methylmercuric chloride/kg body weight was administered subcutaneously to 15 male Wistar rats for 10 days, and the glutathione peroxidase activity in the liver was measured to compare with the control activity. A marked decrease was observed in the glutathione peroxidase activity in the experimental animals, which measured as low as 40% in comparison to that in the control animals. It can be speculated that the inhibition of glutathione peroxidase activity plays a significant role in the development of mercury toxicity and that the protective effect of selenium and vitamin E on the mercury intoxication might be partly due to preserving the glutathione peroxidase activity in the antioxidative defense mechanisms.     

Different change patterns of the isozymes of cytochrome P450 and glutathione S-transferases in chemically induced liver damage in rat.

In this experiment, we studied the different changes in activities and protein levels of each subform of hepatic cytochrome P450 and glutathione S-transferase (GST), in chemical-induced liver injury in rats. Rats were administered 1,1-dichloroethylene (DCE), allyl alcohol (AA), bromobenzene (BB) and N,N-dimethylformamide (DMF) p.o. once every two days for 7 times, and decapitated 18 hr after the last administration. DCE and AA showed stronger hepatic toxicity than BB and DMF, as serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were higher in DCE and AA treated rats than in BB and DMF groups. Anti-cytochrome P450 inhibitable activity of toluene metabolism and/or immunoblot analysis showed that CYP2E1 and CYP2B1/2 were induced by BB and DMF, but not by the other two chemicals; CYP2C11 was greatly decreased by all of the four toxicants; and CYP1A1/2 was slightly reduced by the four treatments. These changes were reflected in testosterone metabolism. Formation of 6 beta- and 7 alpha-hydroxytestosterone from testosterone was enhanced only in DMF-treated rats, whereas that of 2 alpha- and 16 alpha-hydroxytestosterone was reduced by all of the four chemicals. Serum GST activity was increased only in BB and DMF treated rats, but liver cytosolic GST activity was enhanced by all of the four hepatotoxicants, with higher values in BB and DMF groups than in DCE and AA groups. Immunoblot analysis demonstrated that GST Yp was induced by BB and DMF treatments, and Ya and Yc were increased only by BB. GST Yk and Yb1 were not affected by the treatments. The different change patterns of enzymes by a specific toxin and the similar modifying effect on a specific enzyme by different toxins were discussed in relation to the liver damage and to the heterogeneous distribution of enzymes in liver.     

Effect of selenium repletion on glutathione peroxidase protein level in rat liver

We have previously reported that liver glutathione peroxidase (GSH-Px, EC 1.11.1.9) protein level and activity decrease exponentially during Se deficiency. To determine the effect of Se repletion on these parameters, Se-deficient rats were repleted with 0.1 or 0.5 mg Se/kg diet as Na2SeO3 in a 30% torula yeast-based diet and were killed 0, 1, 2, 3, 5, 7 or 14 d later. GSH-Px protein was quantitated using anti-GSH-Px antibodies. Dietary repletion with 0.5 mg Se/kg diet increased GSH-Px protein and activity significantly (P less than 0.05) after 1 d. After 5 d for GSH-Px protein and 7 d for activity the rate of increase slowed, and at d 14 neither GSH-Px protein nor activity was significantly different from that of Se-adequate rats. Repletion with 0.1 mg Se/kg diet did not significantly increase GSH-Px protein or activity until 14 d. To examine the short-term effect of Se repletion, Se-deficient rats were injected intravenously with 15 or 60 micrograms Se as Na2SeO3 and killed 1, 3, 6, 12 or 24 h later. Only rats injected with 60 micrograms Se and killed 24 h later had a significant increase in GSH-Px activity along with a marginally significant increase in GSH-Px protein. These response curves indicate that homeostatic processes control the level of GSH-Px. The lack of an increase in GSH-Px until 24 h after Se administration implies that additional metabolic events after a rise in cellular Se may be necessary prior to an increase in GSH-Px synthesis in Se-deficient rats.     

Salinity effects on activity and expression of glutathione S-transferases in white sturgeon and Chinook salmon

This study evaluated the activity and expression of the glutathione S-transferase (GST) detoxification isoenzymes in juvenile white sturgeon (Acipenser transmontanus) and Chinook salmon (Oncorhynchus tshawytscha) during acclimation from freshwater (2 per thousand) to estuarine (15 per thousand) salinity conditions. In white sturgeon, GST activity toward 1-chloro-2,4-dinitrobenzene (CDNB) increased significantly (P = 0.005; n = 5) with elevated salinity, but not for the Chinook salmon (P = 0.174; n = 10). GST activity of both sturgeon and salmon toward ethacrynic acid (ETHA) did not significantly change with elevated salinity (P = 0.516 with n = 3, and P = 0.125 with n = 3, respectively). Expression of the GST classes, and hepatic glutathione (GSH) concentration, as determined by HPLC, also did not significantly change with increased salinity. In conclusion, overall GST activity in white sturgeon, but not Chinook salmon, is stimulated by elevated water salinity, thus electrophilic chemicals such as pesticides may be more effectively detoxified by sturgeon as they undergo seaward migration.     

中国汉族人口三种谷胱甘肽S-转移酶基因多态性分析

目的：分析中国汉族人口谷胱甘肽S－转移酶（GSTs)基因多态性分布。方法：样本为450名中国汉族人口,采用多重等位基因特异聚合酶链反应（PCR）方法分析GSTM1和GSTT1基因多态性,采用PCR－限制性片段长度多态性方法分析GSTP1＋313核苷酸位点的基因多态性。结果：GSTM1缺失型和GSTT1缺失型基因型频率分别为57％和45％,同时具有GSTM1缺失型和GSTT1缺失型基因型的人个体频率为28．92％;而GSTP1＋313位点G等位基因频率为18．7％,并发现该人群中同时具有3种危险基因型（GSTM1缺失型、GSTT1缺失型和GSTP1＋313A／A）的个体频率为18．04％。GSTs基因型分布不受性别和年龄的影响。结论：中国汉族人口GSTM1、GSTT1和GSTP1基因呈多态性分布,其等位基因和基因型频率不同于其他种族。     

Vitamin C levels in blood are influenced by polymorphisms in glutathione S-transferases

Purpose  

Glutathione S-transferases (GSTs) are intimately involved in combating oxidative stress and in detoxifying xenobiotics. Our objective was to examine possible interactions between polymorphisms in GST genes and plasma vitamin C, tocopherols and carotenoids in 149 reference subjects and 239 subjects occupationally exposed to mineral fibres (asbestos, rock wool, glass fibre), agents that induce oxidative stress.     

Effect of ethanol on the microsomal glutathione S-transferase activity in glutathione-depleted rat liver

Depletion of hepatic glutathione in male rats by starvation caused a significant increase in microsomal glutathione S-transferase activity, which was not affected by acute ethanol pretreatment. An additional depletion in fasted rats by diethylmaleate (0.5 g/kg) caused a further increase in the enzyme activity, but this increase was delayed in ethanol intoxicated rats. Although ethanol caused a small increase in hepatic microsomal lipid peroxidation in control animals, this effect of ethanol was not observed in diethylmaleate treated rats and thus was apparently not responsible for the delay in enzyme activation. It is suggested that the activation of microsomal glutathione S-transferase activity towards 1-chloro-2,4-dinitrobenzene in glutathione-depleted rat liver may be produced by changes in thiol/disulfid ratio and/or some reactive oxygen species.