[转移帖]PLoS ONE：发现HCV诱导胰岛β细胞死亡机制

ms003

原帖由ipsvirus 发表于 2012-6-6 12:31

近日，来自南京医科大学的研究人员发现，丙型肝炎病毒（HCV）诱导了胰岛β细胞通过Caspase 3依赖的信号通路以一种新的凋亡类似的方式死亡。相关研究成果于6月4日在线发表在PLoS ONE上。

流行病学研究已经发现，丙型肝炎病毒(HCV)的感染与2型糖尿病的发展息息相关。已知胰岛β细胞的缺陷是2型糖尿病发展的关键，在该研究中，研究人员利用了病毒感染系统，研究了由HCV所感染的胰岛细胞系MIN6。

研究结果表明，对于MIN6细胞的病变效应，HCV病毒自身是不可缺少的，而且还具有剂量以及时间依赖性。HCV的感染抑制了细胞的增生，并引起MIN6细胞以凋亡特征而死，这些特征包括细胞表面暴露出磷脂酰丝氨酸、线粒体膜电位的降低、caspase 3及多聚(ADP-核糖)聚合酶的激活以及核内DNA的断裂。然而，HCV感染的细胞的细胞核出现膨胀且密度降低，并且这些细胞具有完好的细胞膜及核膜，这表明这是一种新的凋亡类似的细胞死亡形式。

他们还发现，HCV的感染也引起了内质网应激。此外，在MIN6细胞内，他们检测到了HCV RNA的复制，虽然其感染效率极低，并且没有子代病毒粒子产生。

总的来说，该研究结果表明，HCV的感染通过内质网应激及caspase 3相关的特异性通路诱导了胰岛β细胞的死亡。

转自http://www.bioon.com/biology/biomed/525004.shtml

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Hepatitis C Virus Induced a Novel Apoptosis-Like Death of Pancreatic Beta Cells through a Caspase 3-Dependent Pathway

Qian Wang, Jizheng Chen, Yun Wang, Xiao Han, Xinwen Chen.

Epidemiological and experimental studies have suggested that Hepatitis C virus (HCV) infection is associated with the development of type 2 diabetes. Pancreatic beta cell failure is central to the progression of type 2 diabetes. Using virus infection system, we investigate the influence of HCV infection on the fate of the insulinoma cell line, MIN6.Our experiments demonstrate that the HCV virion itself is indispensable and has a dose- and time-dependent cytopathic effect on the cells. HCV infection inhibits cell proliferation and induces death of MIN6 cells with apoptotic characteristics, including cell surface exposure of phosphatidylserine, decreased mitochondrial membrane potential, activation of caspase 3 and poly (ADP-ribose) polymerase, and DNA fragmentation in the nucleus. However, the fact that HCV-infected cells exhibit a dilated, low-density nucleus with intact plasma and nuclear membrane indicates that a novel apoptosis-like death occurs. HCV infection also causes endoplasmic reticulum (ER) stress.Further, HCV RNA replication was detected in MIN6 cells, although the infection efficiency is very low and no progeny virus particle generates. Taken together, our data suggest that HCV infection induces death of pancreatic beta cells through an ER stress-involved, caspase 3-dependent, special pathway.

http://www.plosone.org/article/i ... ournal.pone.0038522