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

  • Sci Rep. 2018 Apr 23;8(1):6379. doi: 10.1038/s41598-018-24414-y.
Mi-Bo Tang  1  2 ,  Yu-Sheng Li  1 ,  Shao-Hua Li  1  2 ,  Yuan Cheng  1  2 ,  Shuo Zhang  1  2 ,  Hai-Yang Luo  1  2 ,  Cheng-Yuan Mao  1 ,  Zheng-Wei Hu  1  2 ,  Jonathan C Schisler  3  4 ,  Chang-He Shi  5 ,  Yu-Ming Xu  6
Affiliations
  • 1. Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China.
  • 2. The Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  • 3. McAllister Heart Institute, Chapel Hill, NC, 27514, USA.
  • 4. Department of Cardiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27514, USA.
  • 5. Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China. [email protected].
  • 6. Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China. [email protected].
PMID: 29686306 DOI: 10.1038/s41598-018-24414-y
Abstract

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.

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