• 대한한방내과학회지
• /
• 제28권3호
• /
• pp.453-463
• /
• 2007

Backgrounds : Glutathione-s-transferase (GST) is a kind of phase II metabolism enzyme and plays an important role in the detoxification of various toxic chemicals. It was reported that the genetic polymorphism of GSTM1 and GSTT1 genes may be responsible for asthma development and susceptibility to allergy. Traditional oriental medicine uses a unique diagnostic technique. differentiation-syndrome. to analyze signs and symptoms of patients synthetically. Through differentiation-syndrome. asthma patients can be divided into two groups: the deficiency syndrome group (DSG) and the excess syndrome group (ESG). Objectives : The purpose of this study was to investigate the possible association of GST gene polymorphism with clinical phenotype by differentiation-syndrome of bronchial asthma patients. Materials and Methods : One hundred and ten participants were evaluated by pulmonary function test. Patients with 53 DSG and 31 ESG by differentiation-syndrome were assessed for genetic analysis. GSTM1 and GSTT1 deletion polymorphism was performed by polymerase chain reaction (PCR). Results : GSTM1 gene deletion was detected in 43.4% of individuals in the DSG and in 38.71 % in the ESG. The distribution of GSTM1 polymorphism between DSG and ESG was not significantly different [$x^2$=0.1767, p=0.6742; OR(95% CI)=1.2139(0.4915-2.9979)]. The proportion of GSTT1 null genotypes was 41.51% in the DGS and 45.16% in the ESG. The distribution of GSTT1 polymorphism between DSG and ESG was also not significantly different [$x^2$=0.1065, p=0.7442; OR(95% CI)=0.8618(0.3525-2.1065)]. In the combined analysis of GSTM1 and GSTT1 genes, the frequency of both null type of GSTM1/GSTT1 genes was not significantly different from both positive type of GSTM1/GSTT1 genes[$x^2$=0.0768, p=0.7817; OR(95% CI)=1.2000(0.3303-4.3602)] Conclusions : These results indicate that polymorphism of the GST gene might not be associated with the symptomatic classification of DSG and ESG by differentiation-syndrome in Korean asthmatics.

• 대한의생명과학회지
• /
• 제6권2호
• /
• pp.101-107
• /
• 2000

Bromobenzene의 투여 간격에 따라 간손상이 어떠한 차이를 나타내는지를 검토하기 위하여 흰쥐에 체중 1 kg 당 400 mg의 bromobenzene을 복강으로 2일 및 1일 간격으로 각각 3회 투여한 다음 간손상을 병리조직학적, 간기능적 측면에서 검토한 결과2일 간격으로 투여한 실험군에서 간손상이 경미하게 나타났다. 그리고 간조직 중 cytochrome P45O 함량은 2일 간격으로 투여 한 실험군에서는 대조군 보다 증가되는 경향을 보였으나 1일 간격으로 투여 한 경우에는 대조군 보다 오히려 유의한 (p<0.01) 감소를 보였다. 간조직 중 대조군에 대한 glutathione 감소율과 glutathione S-transferase 활성 증가율은 2일 간격으로 bromobenzene을 투여한 군이 1일 간격으로 투여한 실험군 보다 높게 나타났다. 이상 실험 결과는 동일한 양과 회수로서 bromobenzene을 격일로 투여한 실험동물에 있어서 매일 투여한 경우 보다 간손상이 경미하였으며, 이는 bromobenzene의 대사율이 증가됨으로서 나타난 결과로 생각된다.

• 한국잡초학회지
• /
• 제16권4호
• /
• pp.327-336
• /
• 1996

DPE계 제초제(除草劑)인 oxyfluorfen의 생리활성(生理活性)을 내성(耐性)으로 선발되었던 벼 3품종(品種)과 감수성(感受性) 벼 4품종(品種)및 피를 공시하여 oxyfluorfen을 처리 후 항산화제(抗酸化劑) 함량과 GST 활성(活性)으로 조사하였다. 1. 식물자체가 보유하는 vitamin C 함량은 내성(耐性) 벼품종(品種)들이 감수성(感受性) 벼품종(品種)들이나 피보다 많았다. Vitamin E, carotenoid 및 glutathione(GSH, GSSG, total glutathione) 함량은 내성(耐性)과 감수성(感受性)식물들간에 양적인 차이를 볼 수 없었다. 2. Oxyfluorfen 처리에 따른 vitamin C 함량은 내성(耐性) 벼품종(品種) Hawon과 Baru에서 감수성(感受性) 벼품종(品種)들과 피보다 감소가 적었다. Oxyfluorfen 처리후 vitamin E 및 GSH 함량은 내성(耐性) 벼품종(品種)들이 감수성(感受性) 벼품종(品種)들이나 피보다 높았다. 그러나 carotenoid 함량은 내성(耐性) 벼품종(品種)들이 감수성(感受性) 벼품종(品種)들보다 높았으나, 감수성(感受性)인 피와는 차이가 없었다. 그리고 GSSG 함량은 내성(耐性)과 감수성종(感受性種)들간 차이가 없었다. 3. CDNB 또는 oxyfluorfen을 기질로 사용했을 때 식물 자체가 보유한 GST 활성(活性)은 내성(耐性) 벼품종(品種)들이 감수성(感受性) 벼품종(品種)들이나 피보다 높았다. 4. Oxyfluorfen 처리후 GST 활성(活性)은 벼에서 유도되지 않았으나, 오히려 피에서는 유도되었다. 또한, 벼의 GST 활성(活性)은 acifluorfen, bifenox 및 oxadiazon 처리에서도 유도되지 않았다.

• Biomolecules & Therapeutics
• /
• 제13권4호
• /
• pp.232-239
• /
• 2005

An aqueous extract of oriental herbal composition named Onchengyeum and curcumin, an antioxidant isolated from turmeric (Curcuma Zonga L.) reduced hepatotoxicity induced by carbon tetrachloride ($CCI_4$). Improved liver function was observed by measuring the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), blood urea nitrogen (BUN), creatinine (CRE), total cholesterol (T-CHO), triglyceride (TG), low density lipoprotein cholesterol (LDL-CHO), high density lipoprotein cholesterol (HDL-CHO), total protein (TP), albumin (ALB) and total bilirubin (BIL) in serum. Hepatic parameters monitored were levels of cholesterol (CHO), triglyceride (TG), and malondialdehyde (MDA) and activities of cytochrome P450 (CYP), NADPH-CYP reductase, superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione S-transferase (GST), glutathione reductase (GR), and glutathione peroxidase (GPx). The histopathological examination showed that the treatment of Onchengyeum and curcumin relieved the ballooning degeneration of hepatocytes which had been generated by $CCI_4$. The results suggested that hepatoprotective effects of Onchengyeum and curcumin possibly are due to their promising antioxidative activity.

• Biomolecules & Therapeutics
• /
• 제14권4호
• /
• pp.207-215
• /
• 2006

Sachungwhan reduced hepatotoxicity induced by carbon tetrachloride($CCl_4$). Improved liver function was observed by measuring the activities of aspartate aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatase(ALP), blood urea nitrogen(BUN), creatinine(CRE), total cholesterol(TCHO), triglyceride(TG), low density lipoprotein cholesterol(LDL-CHO), high density lipoprotein cholesterol(HDL-CHO), total protein(TP), albumin(ALB) and total bilirubin(BIL) in serum. Hepatic parameters monitored were levels of cholesterol(CHO), triglyceride(TG), malondialdehyde(MDA), content of cytochrome P450(CYP), level of glutathione(GSH), and activities of NADPH-CYP reductase, superoxide dismutase(SOD), catalase(CAT), glutathione S-transferase(GST), glutathione reductase(GR), glutathione peroxidase(GPx). The histopathological examination showed that the treatment of Sachungwhan relieved the ballooning degeneration of hepatocytes which had been generated by $CCl_4$. The results suggested that hepatoprotective effects of Sachungwhan possibly are due to their promising antioxidative activity.

• 대한한의학회지
• /
• 제23권3호
• /
• pp.33-42
• /
• 2002

Objective : This study was performed to investigate the activity of Whagan-Jeon (huaganjian) in protection against acetaminophen (AAP)-induced hepatotoxicity and the possible mechanisms in vivo. Methods : The following were performed : Serum ALT, depletion of hepatic glutathione (GSH) levels, the microsomal p. nitrophenol hydroxylation activity, microsomal aniline hydroxylation activity, genomic DNA fragmentation and its reversal, hepatic glutathione-S-transferase (GST) activity, and hepatic NAD(P)H:quinone oxidoreductase (QR) activity Results : Whagan-Jeon (huaganjian) protected against AAP-inducedhepatotoxicity by the increase of GSH levels, inhibition of P450 2E1-specific metabolic activities, attenuation of hepatic DNA damage, and induction of GST and QR activities in vivo. Conclusions : In conclusion, Whagan-Jeon (huaganjian) was effective in protection against AAP-induced hepatoxicity.

• 한국응용약물학회:학술대회논문집
• /
• 한국응용약물학회 1997년도 춘계학술대회
• /
• pp.93-93
• /
• 1997

Analysis of protein is often frustrated by the inability to isolate large amounts of purified protein from a native source. To overcome this problem, fusion protein expression systems such as pGEX system have been widely used. Using pGEX system, the desired protein could be easily obtained in a large amount in E. coli, and then the fusion protein could be used for the study of the function of the given protein. To analyze and purify the GST fusion protein, anti-GST antibody could be used as one of the system of choice. However, the production and characterization of monoclonal anti-GST antibody has not been studied extensively yet. To produce monoclonal anti-GST antibody, GST was purified from E. coli transformed with pGEX-cs, one of the pGEX system and was used as an antigen. The monoclonal antibody was produced by fusion of the immunized spleen cells with SP2-0 myeloma cells. The antibody was characterized by ELISA, western blotting, etc. The monoclonal antibody produced in this study (mAb-GSTA) showed strong and specific immunoreactivity against not only GST but also GST-fusion proteins. Also, mAb-GSTA was successfully used for the immunoaffinity purification of the GST ${\beta}$-Rc.-third intracellular-loop fusion protein. The results of the present study suggest that mAb-GSTA may be used for the identification and purification of GST fusion proteins.

• Journal of Nutrition and Health
• /
• 제50권1호
• /
• pp.10-24
• /
• 2017

본 연구는 건강한 성인 남녀를 대상으로 glutathione S-transferase (GST)M1 및 T1 유전자 다형성에 따라 한식에서 주로 섭취하는 식물성 식품군과 한식 식단의 DNA 손상 감소효과를 측정하여 유전적 민감도가 어떻게 나타나는지를 알아보기 위해 수행되었다. 이를 위하여 건강한 성인 남녀 59명을 대상으로 혈액을 채취하여 GST genotype을 분류하였으며 그 중 17명을 선발하여 DNA 손상 감소효과를 Comet assay를 이용하여 측정하였고 DNA damage relative score로 나타냈다. 제 5기 2차년도 국민건강영양조사를 활용하여 한국인이 많이 섭취하는 식물성 식품을 10가지 식품군 (감자류, 견과류, 곡류, 과일류, 김치류, 두류, 버섯류, 오일류 채소류 해조류)으로 분류 후, 각 식품군별 총 섭취량의 1% 이상을 섭취한 84종의 식품을 한식 식물성 식품으로 최종 선정하였으며 한식 식단 (Korean diet)은 한국영양학회에서 발행한 [2010 한국인 영양섭취 기준]에 제시되어 있는 1주일 표준식단 (2,000 kcal/day)을 사용하였다. GSTM1 유전자 다형성에 따른 한식 식물성 식품군의 Tail moment로 본 DNA 손상 감소효과는 곡류와 오일류에서만 GSTM1 wild type보다 mutant type에서 유의하게 높았다. 이에 비해 DNA 손상 감소 효과를 % DNA in tail과 Tail moment로 본 결과, 견과류 과일류 채소류 버섯류 김치류 해조류에서 GSTT1 mutant type에 비해 wild type에서 유의하게 더 높게 나타났다. GSTM1과 GSTT1의 combined genotype에 따라 한식 식물성 식품의 DNA 손상 감소효과를 본 결과, 과일류, 김치류, 버섯류, 채소류, 해조류는 1군 (GSTM1+/GSTT1+) 및 3군 (GSTM1-/GSTT1+)에서, 오일류는 3군 (GSTM1-/GSTT1+)에서 DNA 손상 감소 효과가 유의하게 높았으며. 감자류, 견과류, 곡류, 두류, Total은 DNA 손상 감소 효과가 2군 (GSTM1+/GSTT1-) 및 3군 (GSTM1-/GSTT1+)에서 유의하게 높아 식품군에 따라 GST 유전자 다형성에 따른 DNA 손상 감소효과가 다르게 나타나는 것을 확인할 수 있었다. 한식 식단은 DNA 손상의 세 가지 지표인 % DNA in tail, Tail moment, Tail length로 측정해본 결과 GSTM1의 경우 wild type에서 mutant type보다 더 크게 나타났으며, GSTT1의 경우는 genotype에 따라 DNA 손상이 달라지는 경향은 있었지만 유의한 차이를 나타내지 않았다. 결론적으로 한식에서 주로 섭취하는 식물성 식품군에서는 식품에 따라 부분적으로 GSTM1은 mutant type에서, GSTT1은 wild type에서 DNA 손상 보호효과가 더 크게 나타났으며, GSTM1과 GSTT1의 combined genotype에 따른 DNA 손상 보호효과는 식품군에 따라 다르게 나타났다. 반면, 한식 식단에서는 DNA 손상 보호효과가 GSTM1 wild type에서 mutant type보다 더 크게 나타났으며, GSTT1 genotype에는 영향을 받지 않는 것으로 나타났다. 이와 같은 결과는 한식 식물성 식품군 및 식사패턴의 항산화 기능 우수성을 증명하는 기초자료가 될 것이며, 나아가 개인별 유전자에 따른 항산화 맞춤영양연구를 시작하는 시발점이 될 수 있을 것이다. 앞으로 GST 유전자 다형성에 따른 한식과 한식 식물성 식품군의 유전적 민감도를 더 명확하게 규명하기 위해서는 대상 인원을 늘려 수행하는 광범위한 연구가 필요할 것으로 보인다.

• Toxicological Research
• /
• 제13권4호
• /
• pp.339-347
• /
• 1997

Disulfiram (DSF) and diethyldithiocarbamate (DDC), a reduced form of DSF, protect the liver against toxicant-induced injury through inhibition of cytochrome P450 2E1. The effect of DSF and DDC on the levels of major hepatic microsomal epoxide hydrolase (mEH) and glutathione S-transferase (GST) expression was comparatively studied, given the view that these enzymes are involved in terminal detoxification events for high energy intermediates of xenobiotics. Treatment of rats with a single dose of DSF (20-200 mg/kg, po) resulted in 2- to 15-fold increases in the mEH mRNA level at 24 hr with the ED$_{50}$ value being noted as 60 mg/kg. The mEH mRNA level was elevated ~15-fold at 24 hr after treatment at the dose of 100 mg/kg, whereas the hepatic mRNA level was rather decreased from the maximum at the dose of 200 mg/kg, indicating that DSF might cause cytotoxicity at the dose. In contrast to the effect of DSF, DDC only minimally elevated the mEH mRNA level at the doses employed. DSF moderately increased the major GST mRNA levels in the liver as a function of dose, resulting in rGSTA2, rGSTA3/5 or rGSTM1 mRNA levels being elevated 3- to 4-fold at 24 hr post-treatment, whereas the rGSTM2 mRNA level was not altered. DDC, however, failed to stimulate the mRNA levels for major GST subunits, indicating that the reduced form of DSF was ineffective in stimulating the GST the expression. The effect of other organosulfides including aldrithiol, 2, 2'-dithiobis(benzothiazole) (DTB), tetramethylthiouram disulfide (TMTD) and allyl disulfide (ADS) on the hepatic mEH and GST mRNA expression was assessed in rats in order to further confirm the increase in the gene expression by other disulfides. Treatment of rats with aldrithiol (100 mg/kg, po) resulted in a 16-fold increase in the mEH mRNA level at 24 hr post-treatment. DTB, TMTD and ADS also caused 5-, 9- and 12-fold increases in the rnRNA level, respectively, as compared to control. Thus, all of the disulfides examined were active in stimulating the mEH gene in the liver. The organosulfides significantly increased the rGSTA2, rGSTA3, rGSTA5 and rGSTM1 mRNA levels at 24 hr after administration. In particular, aldrithiol was very efficient in stimulating the rGSTA and rGSTM genes among the disulfides examined. These results provide evidence that DSF and other sulfides effectively stimulate the mEH and major GST gene expression at early times in the liver and that DDC, a reduced form of DSF, was ineffective in stimulating the expression of the genes, supporting the conclusion that reduced form(s) of organosulfur compound(s) might be less effective in inducing the mEH and GST genes through the antioxidant responsive element(s).

• 한국수의병리학회지
• /
• 제1권1호
• /
• pp.33-39
• /
• 1997

We investigated metabolism and carcinogenesis in livers of Sprague-Dawley rats fed juices and pelleted diets containing Korean native plants petasites japonicus Maxim by evaluating cell localization and expression of cytochrome P450s and GST-P. Anti-cytochrome P450s application in liver sections revealed three to four times increased expression of cytochrome P450E1 immunoreactivity in degenerative hepatocytes when compared to histologically normal hepatocytes. Anti-GST-P in showed positive pren plastic foci as well as in individual hepatocytes randomly scattered throughout all liver sections examined. Additionally GST-P was evident in proliferative endothelial cells and biliary epithelial cells in exposed rat livers. These results suggested that the increased level of cytochrome P4502E1 in affected hepatocytes was a direct consequence of Petasites japonicus toxicity. Further immunoreactivity to anti-GST-P in hepatocytes endothelial cells and biliary epithelial cells indicated a possible preneoplastic effects of Petasites japonicus in Sprague-Dawley rat.