TGF-beta 1 triggers oxidative modifications and enhances apoptosis in hit cells through accumulation of reactive oxygen species by suppression of catalase and glutathione peroxidase
TGF-beta 1 triggers oxidative modifications and enhances apoptosis in hit cells through accumulation of reactive oxygen species by suppression of catalase and glutathione peroxidase
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DOI：
10.1016/s0891-5849(96)00493-5
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发表时间：
1997-01-01
影响因子：
7.4
通讯作者：
Taniguchi, N
中科院分区：
文献类型：
--
作者：
Islam, KN;Kayanoki, Y;Taniguchi, N
转化生长因子-β1（TGF-β1）是一种多功能多肽，与慢性胰腺炎的进展相关。然而，TGF-β1 损伤 β 细胞的机制尚不清楚。在仓鼠胰腺 β 细胞系 (HIT) 中，用 TGF-β 1 处理可增强外源过氧化氢引起的核小体间 DNA 裂解。 TGF-β1 还诱导蛋白质氧化（通过测量蛋白质中的羰基进行评估），并且参与导致脂质过氧化的反应。这最终破坏膜脂并形成丙二醛。我们研究了它对两种主要抗氧化酶：过氧化氢酶和谷胱甘肽过氧化物酶 (GPx) 的影响。 TGF-β1 抑制 mRNA 表达并降低过氧化氢酶和 GPx 的活性。使用过氧化物敏感染料 2',7'-二氯荧光素二乙酸酯进行流式细胞分析判断，TGF-β1 处理的细胞中过氧化氢酶和 GPx 活性的降低导致细胞内过氧化物的增加。这些数据表明，TGF-β1 通过抑制抗氧化酶来增加活性氧的产生，可能会导致细胞损伤和随后的细胞凋亡，并诱发胰腺炎或糖尿病。版权所有 (C) 1997 爱思唯尔科学公司。
Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional polypeptide that is related to the progression of chronic pancreatitis. However, the mechanism of beta-cell damage by TGF-beta 1 is unknown. Treatment with TGF-beta 1 enhanced internucleosomal DNA cleavage caused by exogenous hydrogen peroxide in a hamster pancreatic beta-cell line (HIT). TGF-beta 1 also induced protein oxidation, assessed by measuring carbonyl groups in proteins, and was involved in reactions that lead to lipid peroxidation. This eventually destructs membrane lipids and forms malondialdehyde. We have investigated its effects on two major antioxidative enzymes, catalase and glutathione peroxidase (GPx). TGF-beta 1 suppressed mRNA expression as well as reduced the activities of catalase and GPx. The decrease in the catalase and GPx activities in TGF-beta 1-treated cells resulted in an increase in intracellular peroxides as judged by flow cytometric analysis using a peroxide-sensitive dye, 2',7'-dichlorofluorescin diacetate. These data suggest that the augmented production of reactive oxygen species by TGF-beta 1 through suppression of antioxidative enzymes may cause cellular damage and consequent apoptosis and induce pancreatitis or diabetes. Copyright (C) 1997 Elsevier Science Inc.