Anisomycin prevents OGD-induced necroptosis by regulating the E3 ligase CHIP.
Mi-Bo TangYu-Sheng LiShao-Hua LiYuan ChengShuo ZhangHai-Yang LuoCheng-Yuan MaoZheng-Wei HuJonathan C SchislerChang-He ShiYu-Ming XuPublished in: Scientific reports (2018)
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.
Keyphrases
- cerebral ischemia
- protein kinase
- subarachnoid hemorrhage
- brain injury
- blood brain barrier
- cell death
- circulating tumor cells
- binding protein
- genome wide
- signaling pathway
- poor prognosis
- mesenchymal stem cells
- cell proliferation
- oxidative stress
- cancer therapy
- high glucose
- dna methylation
- endothelial cells
- diabetic rats
- heat shock protein