NLRP3 Inflammasome Is Involved in Q-VD-OPH Induced Necroptosis Following Cerebral Ischemia-Reperfusion Injury View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2018-06

AUTHORS

Xue Teng, Weiwei Chen, Zhihan Liu, Tao Feng, Hui Li, Sheng Ding, Yonggang Chen, Ying Zhang, Xianping Tang, Deqin Geng

ABSTRACT

Necroptosis is a manner of caspase-independent cell death,which accounts for delayed ischemic cerebral injury, and can be used as a novel tool to expand the treatment time window in ischemic cerebral injury. Q-VD-OPH, a novel pan caspase inhibitor, has been identified as an inducer of necroptosis. In this study, we determined the optimal dose of Q-VD-OPH, which induces necroptosis in rats by the middle cerebral artery occlusion, followed by reperfusion. Furthermore, we report that the NLRP3 inflammasome is involved in necroptosis, with levels of NLRP3 inflammasome proteins as well as inflammatory cytokines, such as IL-1β, being elevated. We also demonstrated that NLRP3 was not only expressed in microglia and vascular endothelial cell, but also in neurons when necroptosis is induced with Q-VD-OPH. Inhibition of NLRP3 by glyburide strongly suppressed the expression of NLRP3 inflammasome proteins and IL-1β, and markedly reduced brain tissue damage. Our findings provide evidence that pretreatment with Q-VD-OPH suppresses apoptosis and induces necroptosis in the cerebral ischemia-reperfusion model. We also identified that the NLRP3 inflammasome plays an important role in neuronal necroptosis, and that NLRP3 inflammasome deficiency reduces brain tissue damage after cerebral ischemia-reperfusion injury in rats. More... »

PAGES

1200-1209

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s11064-018-2537-4

    DOI

    http://dx.doi.org/10.1007/s11064-018-2537-4

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1104242287

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29802529


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