• Toxicological Research
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• v.19 no.3
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• pp.181-187
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• 2003

Effects of repeated treatment with butylated hydroxyanisole (BHA) on the induction of glutathione S-transferases (GSTs) and teratogenicity of cyclophosphamide were investigated in rats. Pregnant rats were orally treated with BHA (50 mg/kg) for 7 days, from days 6 to 12 of gestation, and intraperitoneally challenged with cyclophosphamide (15 mg/kg) 2 hr after the final treatment. On day 20 of gestation, the maternal and fetal abnormalities were examined. Separately, a part of rats was sacrificed for the assay of hepatic and placental GSTs activities on day 12 of gestation following 7-day treatment with BHA. Cyclophosphamide, administered on day 12 of gestation, induced 43.2% of fetal death and resorption, and 100% of malformations in live fetuses, in contrast to low fetal resorption (8.7%) and malformations (8%) in control group. The malformations include cranial defect and exencephaly (100%), micrognathia and tongue extrusion (100%), limb defects (40%), renal pelvic dilatation (39%), and cleft palate (15%). Interestingly, BHA induced GSTs activities by 62% and 46% over the control in liver and placenta, respectively, and remarkably reduced the fetal resorption (13.9%) and malformations, resulting in 62% of cranial defect and exencephaly, 68% of micrognathia and tongue extrusion, 29% of limb defects, and 14% of renal pelvic dilatation. Taken together, it is suggested that a long-term pretreatment with BHA could substantially prevent fetuses from abortion and malformations following intrauterine exposure to teratogens including cyclophosphamide by inducing phase II antioxidant enzymes such as GSTs.

• Environmental Analysis Health and Toxicology
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• v.13 no.3_4
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• pp.55-61
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• 1998

Glutathione-S-transferases (GSTs) detoxify electrophilic xenobiotics and reactive metabolites. Recently benzene-fused heterocycles have been shown to increase the total amount of hepatic GSTs in rats. Primarily this study aimed to determine the induction of GSTs by benzoazoles (BAs) including benzoxazole (BX), 2-methylbenzoxazole (M-BX), 2,5-dimethyl benzoxazole (D-BX), benzothiazole (BT), aminobenzothiazole (A-BT) and 2-mercaptobenzothiazole (M-BT) in rats. Hepatic cytosol and poly(A)$^+$ mRNA were prepared from rats after oral administration of BX, BT, M-BX, D-BX, A-BT and M-BT for 5 consecutive days at doses of 1 mmol/kg. Western immunoblot and northern blot analysis were conducted with rabbit anti-GST Ya, Yb$_1$, Yb$_2$, Yc antibodies and cDNA probes containing = 500 bps in the specific coding regions of Ya, Yb$_1$, Yb$_2$, Yc$_1$, and Yc$_2$, respectively. All BAs increased the amount of enzymes and mRNA levels of GSTs. BT was the most effective inducer of GSTs among the compounds examined in this study. Although A-BT and M-BT, the derivatives of BT, induced GSTs, these chemicals had lesser effect on induction of GSTs than BT. The derivatives of BX also induced less GSTs than the parent compound and the addition of methyl group to the benzene ring of BX reduced the induction of GSTs. BAs had better inductive effects on the class $\alpha$(Ya, Yc) than class $\mu$ GSTs (Yb$_1$, Yb$_2$). BAs enhanced mRNA levels of GSTs in parallel with the protein levels. These results indicate that 1) most of BAs induced various isozymes of GSTs, 2) the induction of GSTs appears to be correlated with the chemical structure of the derivatives, and 3) the expression of GST by BAs is presumably under the transcriptional regulation.

• Journal of Crop Science and Biotechnology
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• v.10 no.1
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• pp.19-26
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• 2007

Glutathione S-transferases(GSTs, EC 2.5.1.18), glyoxalase-I(EC 4.4.1.5) and alliin lyase(alliinase, EC 4.4.1.4) are important enzyme systems in plant bodies. The first two are mainly detoxifying enzymes that utilize glutathione(GSH) in the defense mechanism, and the last one is mainly involved in secondary metabolism and relevant to sulfur compounds derived from GSH. The activities of the three enzymes have been investigated in soluble extracts of vegetable crops, including pumpkin, cabbage, broccoli, radish, carrot, potato, sweet potato, mungbean, and onion. GST activities were detected in all of the vegetables, and the extract of onion bulb exhibited the highest specific activity(648 nmol/min/mgP). The putative GSTs of most of the vegetables were found to be induced by ethanol. The activities of GSTs in onion bulb were found to be markedly inhibited by S-hexyl glutathione and were also inhibited by S-butyl glutathione and S-propyl glutathione. The anti-CmGSTF1 antiserum recognized a thick band for putative onion GST. The estimated glyoxalase-I activity level was also high in onion bulb(4540 nmol/min/mgP), indicating that the thick band detected by Western blot analysis might result from partial recognition of glyoxalase-I by the antiserum. The specific activities for glyoxalase-I were moderate in radish and carrot, and the extracts of other vegetables had rather low levels of activities. The extract of onion also showed the highest specific activity level for alliinase(2069nmol pyruvate/mgP). The extracts of other vegetables also had alliinase activities, although the estimated values were much lower than that of onion.

• Korean Journal of Environmental Agriculture
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• v.16 no.4
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• pp.365-372
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• 1997

Biochemical characteristics and activities of glutathione-S-transferases(GSTs) and carboxylesterase extracted from soybean and corn plants treated with quizalofop-ethyl were investigated. Km value and Vmax of GSTs extracted from soybean and corn plants were $6.7{\times}10^{-3}M$ nmole/mg/min, 50, 20 nmole/mg/min, respectively. Optimum pH of carboxylesterase from soybean and corn was 7.0. Km value and Vmax of carboxylesterase extracted from soybean and corn plants were $4.2{\times}10^{-4}M$, $2.5{\times}10^{-4}M$ nmole/mg/min, 33, 10 nmole/mg/min, respectively. GSTs and carboxylesterase activity were reduced by quizalofop-ethyl. GSTs and carboxylesterse activity of corn was more reduced than that of soybean. When soybean and corn were treated by 80 ppm of quizalofopethyl. Soybean recovered after 10 days elapsing, but corn withered after 3days elapsing.

• Toxicological Research
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• v.23 no.2
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• pp.127-133
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• 2007

Metformin is a drug used to lower blood sugar levels in patients with type 2 diabetes via activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK). The primary objective of this study was to investigate whether metformin at the pharmacologically effective concentrations affects the expressions of ${\gamma}$-glutamylcysteine synthetase and phase II antioxidant genes in the H4IIE cell. Treatment of the cells with either metformin or 5-aminoimidazole-4-carboxamide riboside (AICAR) abrogated tert-butylhydroxyquinone (t-BHQ) induction of ${\gamma}$-glutamylcysteine synthetase, a rate limiting enzyme of GSH synthesis. The ability of t-BHQ to induce glutathione S-transferases (GSTs), a major class of phase II detoxifying enzymes that playa critical role in protecting cells from oxidative stress or electrophiles, was also inhibited by the agents. Transcriptional gene repression by metformin was verified by the GSTA2 promoter luciferase assay. Moreover, either metformin or AICAR treatment significantly decreased t-BHQ-dependent induction of other GSTs (i.e., $GST{\mu}$ and $GST{\pi}$ forms). Taken together, our data indicate that metformin treatment may result in the repression of ${\gamma}$-glutamylcysteine synthetase and glutathione S-transferase genes possibly via AMPK activation.

• Journal of Crop Science and Biotechnology
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• v.11 no.3
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• pp.187-192
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• 2008

The effects of some coumarins(coumarin, 7-hydroxycoumarin, scopoletin and esculetin) were investigated on pumpkin(Cucurbita maxima Duch.) seedlings and on pumpkin glutathione S-transferases(GSTs). Coumarin and esculetin suppressed the growth of seedlings, especially the elongation of roots as well as hypocotyls. Among the compounds tested, only esculetin inhibited the activity of a particular pumpkin GST by 50%, CmGSTU3 toward 1-chloro-2, 4- dinitrobenzene(CDNB) and at a concentration of 22 ${\mu}M$. Both ethylacetae(EtOAc) and water fractions in pumpkin seedlings and different organs of one-month-old pumpkin plants contained esculetin or similar hydrophobic fluorescent substances as well as hydrophilic substances, which showed different degrees of inhibitory effects on CmGSTU3 activity.

• Proceedings of the Korean Society of Sericultural Science Conference
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• 2003.04a
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• pp.68-68
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• 2003

The glutathione-S-transferases (GSTs) are enzymes responsible for the protection of cells from chemical toxicants and oxidative stress. In insects, GSTs have been particularly known to be implicated in the resistance to insecticides. In this study, a cDNA encoding the GST gene homologue was isolated from the cDNA library of the mole cricket, Gryllotalpa orientalis. (omitted)

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.1
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• pp.157-163
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• 2012

Objective: Glutathione S-transferases (GSTs) are multifunctional enzymes that play a crucial role in the detoxification of both the endogenous products of oxidative stress and exogenous carcinogens. Recent studies investigating the association between genetic polymorphisms in GSTs and the risk of adult brain tumors have reported conflicting results. The rationale of this pooled analysis was to determine whether the presence of a GST variant increases adult glioma susceptibility by combining data from multiple studies. Methods: In our meta-analysis, 12 studies were identified by a search of the MEDLINE, HIGHWIRE, SCIENCEDIRECT and EMBASE databases. Of those 12, 11 evaluated GSTM1, nine evaluated GSTT1 and seven evaluated GSTP1 Ile105Val. Between-study heterogeneity was assessed using ${\chi}^2$-based Q statistic and the $I^2$ statistic. Crude odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to estimate the association between GSTM1, GSTT1 and GSTP1 polymorphisms and the risk of adult gliomas. Results: The quantitative synthesis showed no significant evidence to indicate an association exists between the presence of a GSTM1, GSTT1 or GSTP1 Ile105Val haplotype polymorphism and the risk of adult gliomas (OR, 1.008, 1.246, 1.061 respectively; 95% CI, 0.901-1.129, 0.963-1.611, 0.653-1.724 respectively). Conclusions: Overall, this study did not suggest any strong relationship between GST variants or related enzyme polymorphisms and an increased risk of adult gliomas. Some caveats include absence of specific raw information on ethnic groups or smoking history on glioma cases in published articles; therefore, well-designed studies with a clear stratified analysis on potential confounding factors are needed to confirm these results.

• Journal of Plant Biotechnology
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• v.35 no.4
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• pp.265-274
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• 2008

Glutathione S-transferases (GSTs) are multifunctional proteins encoded by a large gene family divided into Phi, Tau, Theta, Zeta, Lambda and DHAR classes on the basis of sequence identity. The Phi(F) and Tau(U) classes are plant-specific and ubiquitous. Their roles have been defined as herbicide detoxification and responses to biotic and abiotic stresses. Fifty-two members of the GST super-family were identified in the Arabidopsis thaliana genome, 13 members of which belong to the Phi class of GSTs (AtGSTFs). Based on the sequence similarities of AtGSTFs, 11 BAC clones were identified from Brassica rapa. Seven unique sequences of ORFs designated the Phi class candidates of GST derived from B. rapa (BrGSTFs) were detected from these 11 BAC clones by blast search and sequence alignment. Some of BrGSTFs were present in the same BAC clones indicating that BrGSTFs could also be clustered as usual in plant. They were mapped on B. rapa linkage group 2, 3, 9 and 10 and their nucleotide and amino acid sequences were highly similar to those of AtGSTFs. In addition, in silico analysis of BrGSTFs using Korea Brassica Genome Project 24K oligochip and microarray database for cold, salt and drought stresses revealed 15 unigenes to be highly similar to AtGSTFs and six of these were identical to one of BrGSTFs identified in the BAC clones indicating their expression. The sequences of BrGSTFs and unigenes identified in this study will facilitate further studies to apply GST genes to medical and agriculture purposes.

• Environmental Analysis Health and Toxicology
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• v.21 no.3 s.54
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• pp.245-253
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• 2006

We reported previously that glucagon decreased alpha- and pi-class glutathione S-transferases (GSTs) and microsomal epoxide hydrolase (mEN) protein levels in primary cultured rat hepatocytes. The present study examines the effects of Protein kinase A (PKA) inhibitor, KT5720, on the glucagon-mediated decrease in expression of GSTs and mEN. To assess cell viability. lactate dehydrogenase release and MTT activity were examined in hepatocytes treated KT5720. Cell viability was significantly decreased in a concentration dependent manner after incubation with KT5720 at the concentrations of 1 $\mu$M or above for 24 h, which was inhibited by the cytochrome P450 inhibitor SKF-525A. In contrast, another PKA inhibitor H89 (up to 25 $\mu$M) was not toxic to hepatocytes. The glucagon-mediated decrease in expression of alpha- and pi-class GSTs and mEH was completely inhibited by 25 $\mu$M H89 and attenuated by 0.1 $\mu$M KT5720. This study demonstrates that KT5720 may cause cytotoxicity in rat hepatocytes through cytochrome P450-dependent bioactivation. The present study implicates PKA in mediating the inhibitory effect of glucagon on expression of alpha- and pi- class GSTs and mEH.