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

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...

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Bibliographic Details
Published in:Scientific reports 2018-04, Vol.8 (1), p.6379-12, Article 6379
Main Authors: Tang, Mi-bo, Li, Yu-sheng, Li, Shao-hua, Cheng, Yuan, Zhang, Shuo, Luo, Hai-yang, Mao, Cheng-yuan, Hu, Zheng-wei, Schisler, Jonathan C., Shi, Chang-he, Xu, Yu-ming
Format: Article
Language:English
Subjects:
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Animals
Anisomycin
Anisomycin - pharmacology
Anti-Bacterial Agents - pharmacology
Apoptosis
c-Jun protein
Cell death
Cell Hypoxia
Female
Gene Expression Regulation, Enzymologic
Glucose - deficiency
Hsc70 protein
Humanities and Social Sciences
Ischemia
JNK protein
Kinases
Mice
multidisciplinary
Necroptosis
Necrosis
Neuroblastoma - etiology
Neuroblastoma - pathology
Neuroblastoma - prevention & control
Oxygen - metabolism
Protein biosynthesis
Protein kinase
Protein synthesis
Proteins
Rats
Rats, Sprague-Dawley
Science
Transcription factors
Ubiquitin
Ubiquitin - metabolism
Ubiquitin-protein ligase
Ubiquitin-Protein Ligases - genetics
Ubiquitin-Protein Ligases - metabolism
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-018-24414-y