Anisomycin 通过调节 E3 连接酶 CHIP 来预防 OGD 诱导的坏死性细胞死亡。

Anisomycin prevents OGD-induced necroptosis by regulating the E3 ligase CHIP.

机构信息

Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China.

The Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

出版信息

Sci Rep. 2018 Apr 23;8(1):6379. doi: 10.1038/s41598-018-24414-y.

Necroptosis is an essential pathophysiological process in cerebral ischemia-related diseases. Therefore, targeting necroptosis may prevent cell death and provide a much-needed therapy. Ansiomycin is an inhibitor of protein synthesis which can also activate c-Jun N-terminal kinases. The present study demonstrated that anisomycin attenuated necroptosis by upregulating CHIP (carboxyl terminus of Hsc70-interacting protein) leading to the reduced levels of receptor-interacting protein kinase 1 (RIPK1) and receptor-interacting protein kinase 3 (RIPK3) proteins in two in vitro models of cerebral ischemia. Further exploration in this research revealed that losing neither the co-chaperone nor the ubiquitin E3 ligase function of CHIP could abolish its ability to reduce necroptosis. Collectively, this study identifies a novel means of preventing necroptosis in two in vitro models of cerebral ischemia injury through activating the expression of CHIP, and it may provide a potential target for the further study of the disease.

细胞坏死是与脑缺血相关疾病的重要病理生理过程。因此，针对细胞坏死可能预防细胞死亡并提供急需的治疗方法。放线菌酮是一种蛋白质合成抑制剂，也可以激活 c-Jun N 端激酶。本研究表明，放线菌酮通过上调 CHIP（热休克蛋白 70 相互作用蛋白羧基末端）来减轻细胞坏死，从而降低两种体外脑缺血模型中受体相互作用蛋白激酶 1（RIPK1）和受体相互作用蛋白激酶 3（RIPK3）蛋白的水平。本研究的进一步探索表明，丧失 CHIP 的共伴侣或泛素 E3 连接酶功能都不能使其丧失减轻细胞坏死的能力。总的来说，这项研究通过激活 CHIP 的表达，确定了一种在两种体外脑缺血损伤模型中预防细胞坏死的新方法，它可能为该疾病的进一步研究提供一个潜在的靶点。