BRCC3 mediates inflammation and pyroptosis in cerebral ischemia/reperfusion injury by activating the NLRP6 inflammasome

作者全名："Huang, Xiaohuan; Tan, Junyi; Ji, Yanyan; Luo, Jing; Zhao, Yong; Zhao, Jing"

作者地址："[Huang, Xiaohuan; Ji, Yanyan; Luo, Jing; Zhao, Yong] Chongqing Med Univ, Dept Pathol, Chongqing, Peoples R China; [Huang, Xiaohuan] Chongqing Three Gorges Med Coll, Dept Pathol, Wanzhou, Peoples R China; [Tan, Junyi; Zhao, Jing] Chongqing Med Univ, Dept Pathophysiol, Chongqing, Peoples R China; [Luo, Jing] Chongqing Med Univ, Affiliated Hosp 1, Dept Neurol, Chongqing, Peoples R China; [Zhao, Yong] Chongqing Med Univ, Dept Pathol, Chongqing 400016, Peoples R China; [Zhao, Jing] Chongqing Med Univ, Dept Pathophysiol, Rd 1, Chongqing, Peoples R China"

通信作者："Zhao, Y (通讯作者)，Chongqing Med Univ, Dept Pathol, Chongqing 400016, Peoples R China.; Zhao, J (通讯作者)，Chongqing Med Univ, Dept Pathophysiol, Rd 1, Chongqing, Peoples R China."

来源：CNS NEUROSCIENCE & THERAPEUTICS

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001192175900001

JCR分区：Q1

影响因子：5.5

年份：2024

卷号：30

期号：3

开始页：　

结束页：　

文献类型：Article

关键词：BRCC3; cerebral I/R injury; neuroinflammation; NLRP6 inflammasome; pyroptosis

摘要："Aims: Neuroinflammation and pyroptosis are key mediators of cerebral ischemia/reperfusion (I/R) injury-induced pathogenic cascades. BRCC3, the human homolog of BRCC36, is implicated in neurological disorders and plays a crucial role in neuroinflammation and pyroptosis. However, its effects and potential mechanisms in cerebral I/R injury in mice are unclear. Methods: Cellular localization of BRCC3 and the interaction between BRCC3 and NLRP6 were assessed. Middle cerebral artery occlusion/reperfusion (MCAO) and oxygen-glucose deprivation/reoxygenation (OGD/R) models were established in mice and HT22 cells, respectively, to simulate cerebral I/R injury in vivo and in vitro. Results: BRCC3 protein expression peaked 24 h after MCAO and OGD/R. BRCC3 knockdown reduced the inflammation and pyroptosis caused by cerebral I/R injury and ameliorated neurological deficits in mice after MCAO. The effects of BRCC3 on inflammation and pyroptosis may be mediated by NLRP6 inflammasome activation. Moreover, both BRCC3 and its N- and C-terminals interacted with NLRP6, and both BRCC3 and its terminals reduced NLRP6 ubiquitination. Additionally, BRCC3 affected the interaction between NLRP6 and ASC, which may be related to inflammasome activation. Conclusion: BRCC3 shows promise as a novel target to enhance neurological recovery and attenuate the inflammatory responses and pyroptosis caused by NLRP6 activation in cerebral I/R injury."

基金机构：National Natural Science Foundation of China

基金资助正文：No Statement Available