Zhu Hong, Zhang Li, Trush Michael A, Li Yunbo
Department of Internal Medicine and Davis Heart & Lung Research Institute, The Ohio State University College of Medicine and Public Health, 473 West 12th Avenue, Columbus, OH 43210, USA.
Free Radic Res. 2007 Feb;41(2):242-50. doi: 10.1080/10715760601009586.
This study was undertaken to investigate the inducibility of glutathione (GSH), glutathione reductase (GR) and glutathione peroxidase (GPx) by 3H-1,2-dithiole-3-thione (D3T) in beta-cells, and the resultant cytoprotection against oxidant injury. Incubation of the insulin-secreting RINm5F cells with D3T led to significant induction of GSH, GR and GPx. D3T-mediated induction of GSH was abolished by buthionine sulfoximine (BSO), suggesting a critical involvement of gamma-glutamylcysteine ligase (gammaGCL). Consistently, incubation of RINm5F cells with D3T resulted in increased expression of gammaGCL protein and mRNA. Pretreatment of RINm5F cells with D3T provided remarkable protection against oxidant-elicited cytotoxicity. On the other hand, depletion of cellular GSH by BSO sensitized RINm5F cells to oxidant injury. Furthermore, cotreatment of RINm5F cells with BSO to reverse D3T-mediated GSH induction abolished the cytoprotective effects of D3T on oxidant injury. Taken together, this study demonstrates that upregulation of glutathione system by D3T is effective for protecting against oxidative beta-cell injury.
本研究旨在探讨3H-1,2-二硫杂环戊烯-3-硫酮（D3T）对β细胞中谷胱甘肽（GSH）、谷胱甘肽还原酶（GR）和谷胱甘肽过氧化物酶（GPx）的诱导作用，以及由此产生的对氧化损伤的细胞保护作用。用D3T孵育胰岛素分泌型RINm5F细胞可导致GSH、GR和GPx的显著诱导。丁硫氨酸亚砜胺（BSO）消除了D3T介导的GSH诱导作用，提示γ-谷氨酰半胱氨酸连接酶（γGCL）起关键作用。同样，用D3T孵育RINm5F细胞导致γGCL蛋白和mRNA表达增加。用D3T预处理RINm5F细胞可显著保护其免受氧化剂诱导的细胞毒性。另一方面，BSO消耗细胞内GSH使RINm5F细胞对氧化损伤敏感。此外，用BSO共同处理RINm5F细胞以逆转D3T介导的GSH诱导作用，消除了D3T对氧化损伤的细胞保护作用。综上所述，本研究表明D3T上调谷胱甘肽系统对保护β细胞免受氧化损伤有效。
