کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2048632 | 1074086 | 2011 | 7 صفحه PDF | دانلود رایگان |
Nitric oxide (NO) has been implicated in pancreatic β-cell death in the development of diabetes. The mechanisms underlying NO-induced β-cell death have not been clearly defined. Recently, receptor-interacting protein-1 (RIP1)-dependent necrosis, which is inhibited by necrostatin-1, an inhibitor of RIP1, has emerged as a form of regulated necrosis. Here, we show that NO donor-induced β-cell death was inhibited by necrostatin-1. Unexpectedly, however, RIP1 knockdown neither inhibited cell death nor altered the protective effects of necrostatin-1 in NO donor-treated β-cells. These results indicate that NO donor induces necrostatin-1-inhibitable necrotic β-cell death independent of RIP1. Our findings raise the possibility that NO-mediated β-cell necrosis may be a novel form of signal-regulated necrosis, which play a role in the progression of diabetes.
► Nitric oxide (NO) donor-induced pancreatic β-cell death was inhibited by Nec-1, a RIP1 inhibitor.
► RIP1 is, however, not required for β-cell death by NO donor and the protective effects of Nec-1.
► These findings provide evidence that NO can mediate Nec-1-inhibitable necrotic β-cell death independent of RIP1.
Journal: FEBS Letters - Volume 585, Issue 19, 3 October 2011, Pages 3058–3064