• 제목/요약/키워드: GSTA2

검색결과 18건 처리시간 0.021초

Repression of γ-Glutamylcysteine Synthetase and Glutathione S-Transferases by Metformin, an Anti-diabetic Agent, in H4IIE Rat Hepatocytes

  • Bae, Eun-Ju;Cho, Min-Joo;Kim, Sang-Geon
    • Toxicological Research
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    • 제23권2호
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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.

PHOSPHATIDYLINOSITOL 3-KINASE REGULATES NUCLEAR TRANSLOCATION OF Nrf2 THROUGH ACTIN REARRANGEMENT

  • Kim, Sang-Geon;Kang, Keon-Wook;Lee, Seung-Jin;Park, Jeong-Weon;Kim, Hye-Jung
    • 한국독성학회:학술대회논문집
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    • 한국독성학회 2002년도 Current Trends in Toxicological Sciences
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    • pp.82-82
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    • 2002
  • Expression of phase II detoxifying genes is regulated by Nrf2-mediated antioxidant response element (ARE) activation. We previously showed that phosphatidylinositol 3-kinase (PI3-kinase) plays an essential role in ARE-mediated rGSTA2 induction by oxidative stress.(omitted)

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Antioxidant mechanism of black garlic extract involving nuclear factor erythroid 2-like factor 2 pathway

  • Ha, Ae Wha;Kim, Woo Kyoung
    • Nutrition Research and Practice
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    • 제11권3호
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    • pp.206-213
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    • 2017
  • BACKGROUN/OBJECTIVES: Although studies have revealed that black garlic is a potent antioxidant, its antioxidant mechanism remains unclear. The objective of this study was to determine black garlic's antioxidant activities and possible antioxidant mechanisms related to nuclear factor erythroid 2-like factor 2 (Nrf2)-Keap1 complex. METHODS/MATERIALS: After four weeks of feeding rats with a normal fat diet (NF), a high-fat diet (HF), a high-fat diet with 0.5% black garlic extract (HF+BGE 0.5), a high-fat diet with 1.0% black garlic extract (HF+BGE 1.0), or a high-fat diet with 1.5% black garlic extract (HF+BGE 1.5), plasma concentrations of glucose, insulin,homeostatic model assessment of insulin resistance (HOMA-IR) were determined. As oxidative stress indices, plasma concentrations of thiobarbituric acid reactive substances (TBARS) and 8-isoprostaglandin $F2{\alpha}$ (8-iso-PGF) were determined. To measure antioxidant capacities, plasma total antioxidant capacity (TAC) and activities of antioxidant enzymes in plasma and liver were determined. The mRNA expression levels of antioxidant related proteins such as Nrf2, NAD(P)H: quinone-oxidoreductase-1 (NQO1), heme oxygenase-1 (HO-1), glutathione reductase (GR), and glutathione S-transferase alpha 2 (GSTA2) were examined. RESULTS: Plasma glucose level, plasma insulin level, and HOMA-IR in black garlic supplemented groups were significantly (P < 0.05) lower than those in the HF group without dose-dependent effect. Plasma TBARS concentration and TAC in the HF+BGE 1.5 group were significantly decreased compared to those of the HF group. The activities of catalase and glutathione peroxidase were significantly (P < 0.05) increased in the HF+BGE 1.0 and HF+BGE 1.5 groups compared to those of the HF group. The mRNA expression levels of hepatic Nrf2, NQO1, HO-1, and GSTA2 were significantly (P < 0.05) increased in the HF with BGE groups compared to those in the HF group. CONCLUSIONS: The improvements of blood glucose homeostasis and antioxidant systems in rats fed with black garlic extract were related to mRNA expression levels of Nrf2 related genes.

THE ESSENTIAL ROLE OF PHOSPHATIDYLINOSITOL 3-KINASE IN THE INDUCTION OF MICROSOMAL EPOXIDE HYDROLASE

  • Kang, Keon-Wook;Ryu, Ji-Hwa;Kim, Sang-Geon
    • 한국독성학회:학술대회논문집
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    • 한국독성학회 2001년도 International Symposium on Signal transduction in Toxicology
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    • pp.140-140
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    • 2001
  • We have shown that PI3-kinase played an essential role in the ARE-mediated rGSTA2 induction by oxidative stress following sulfur amino acid deprivation (SAAD) (Kang et al., Mol. Pharmacol., 2000). Microsomal epoxide hydrolase (mEH), which detoxifies a variety of epoxide intermediates produced from various xenobiotics, is inducible by oxidative stress.(omitted)

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신지명사십리 해수욕장에서 현장조사에 의한 해빈변화와 퇴적물이동 특성 (Characteristics of Beach Change and Sediment Transport by Field Survey in Sinji-Myeongsasimni Beach)

  • 정승명;박일흠
    • 해양환경안전학회지
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    • 제27권5호
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    • pp.594-604
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    • 2021
  • 신지명사십리 해수욕장에서 해빈침식의 원인을 파악하기 위해, 2019년 3월부터 2020년 3월까지 조석, 조류 및 파랑과 같은 외력과 표층퇴적물에 대한 현장조사가 계절별로 수행되었다. 그리고 이들 외력에 반응하는 해빈의 변화양상을 파악하기 위해, 정기적으로 해안선 및 해빈표고가 측량되었고, 과거에 간헐적으로 수행되었던 측량자료도 분석에 활용되었다. 대상해역에서 조류는 해빈변화에 영향을 줄 만큼 충분하지 않았으나, 남측으로 열려있는 이 해역에서 유의파고 1m 이상의 입사파들은 모두 S ~ SE 파향으로 춘하추계에 출현하였으며, 유의파고 2m 이상의 고파랑은 하추계에 태풍의 영향으로 나타났다. 이에 따라 태풍의 영향이 2년 동안 없었던 2018년 7월의 해빈면적은 2019년 3월에 비해 30,138m2 증가해 있었고, 이후 2차례의 태풍의 영향을 겪었던 2020년 3월은 해빈면적이 61,210m2가 줄어든 것으로 나타났다. 그리고 2018년 7월 이후 2차례의 태풍 내습이 있었던 2019년 3월은 5.4%의 해빈체적이 감소한 상태였고, 이후 2019년 9월까지 다시 2차례의 태풍내습에 의해 해빈체적이 7.3% 감소하였으며, 2020년 3월은 해빈체적이 4.4% 감소로서 추동계동안 다소 회복되는 경향을 보였다. GSTA에 의한 퇴적물 이동벡터는 해빈중앙의 소하천으로 부터 토사가 약하게 유입되며, 서측해빈에서 이동경향은 두드러지게 나타나지 않으나, 동측해빈에서 육상역의 토사가 바다쪽으로 그리고 동측에서 서측으로 퇴적물이 이동하는 경향이 아주 우세하게 나타났다. 이러한 퇴적물 이동경향벡터는 해빈에 대해 반시계방향으로 24° 기울어져 있어 연평균파향의 파랑이 입사할 때 서향의 해빈류가 발달하는 것으로 설명할 수 있었다. 이에 따라 서측해빈역은 모래가 풍성하지만, 동측해빈역은 표사공급원의 부재로 자갈이 드러나고 곳곳에 사구포락이 발생하는 것과 같은 침식이 심각하였다. 따라서, 이같은 토사이동구조를 가진 동측해빈역에 양빈과 같은 새로운 표사원을 조성하고, 동측해안 끝단역에서 입사파를 저감시키는 것과 같은 노력이 필요할 것으로 판단되었다.

Phosphatidylinositol 3-Kinase Regulates Nuclear Translocation of NF-E2-Related Factor 2 through Actin Rearrangement in Response to Oxidative Stress

  • Kang, Keon-Wook;Lee, Seung-Jin;Park, Jeong-Weon;Kim, Sang-Geon
    • 대한약학회:학술대회논문집
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    • 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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    • pp.241.3-242
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    • 2002
  • Expression of phase II detoxifying genes is regulated by NF-E2-related factor 2 (Nrf2)-mediated antioxidant response element (ARE) activation. Phosphatidylinositol 3-kinase (PI3-kinase) plays an essential role in ARE-mediated rGSTA2 induction by oxidative stress and controls microfilaments and translocation of actin-associated proteins. This study was designed to investigate the P13-kinase-mediated nuclear translocation of Nrf2 and the interaction of Nrf2 with actin. (omitted)

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