气候变化领域集成服务门户(CCPortal): TAX1BP1 protects against myocardial infarction-associated cardiac anomalies through inhibition of inflammasomes in a RNF34/MAVS/NLRP3-dependent manner

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DOI	10.1016/j.scib.2021.01.030
	TAX1BP1 protects against myocardial infarction-associated cardiac anomalies through inhibition of inflammasomes in a RNF34/MAVS/NLRP3-dependent manner
	Xu H.; Yu W.; Sun S.; Li C.; Ren J.; Zhang Y.
发表日期	2021
ISSN	20959273
起始页码	1669
结束页码	1683
卷号	66 期号:16
英文摘要	Acute myocardial infarction (MI), one of the most common cardiovascular emergencies, is a leading cause of morbidity and mortality. Ample evidence has revealed an essential role for inflammasome activation and autophagy in the pathogenesis of acute MI. Tax1-binding protein 1 (TAX1BP1), an adaptor molecule involved in termination of proinflammatory signaling, serves as an important selective autophagy adaptor, but its role in cardiac ischemia remains elusive. This study examined the role of TAX1BP1 in myocardial ischemic stress and the underlying mechanisms involved. Levels of TAX1BP1 were significantly downregulated in heart tissues of patients with ischemic heart disease and in a left anterior descending (LAD) ligation-induced model of acute MI. Adenovirus carrying TAX1BP1 was delivered into the myocardium. The acute MI induced procedure elicited an infarct and cardiac dysfunction, the effect of which was mitigated by TAX1BP1 overexpression with little effect from viral vector alone. TAX1BP1 nullified acute MI-induced activation of the NLRP3 inflammasome and associated mitochondrial dysfunction. TAX1BP1 overexpression suppressed NLRP3 mitochondrial localization by inhibiting the interaction of NLRP3 with mitochondrial antiviral signaling protein (MAVS). Further investigation revealed that ring finger protein 34 (RNF34) was recruited to interact with TAX1BP1 thereby facilitating autophagic degradation of MAVS through K27-linked polyubiquitination of MAVS. Knockdown of RNF34 using siRNA nullified TAX1BP1 yielded protection against hypoxia-induced MAVS mitochondrial accumulation, NLRP3 inflammasome activation and associated loss of mitochondrial membrane potential. Taken together, our results favor a cardioprotective role for TAX1BP1 in acute MI through repression of inflammasome activation in a RNF34/MAVS-dependent manner. © 2021 Science China Press
关键词	Acute myocardial infarction Autophagic degradation Mitochondrial antiviral signaling protein NLRP3 inflammasome RNF34 TAX1BP1
英文关键词	Cardiology; Cell death; Cell membranes; Chemical activation; Diseases; Heart; Mitochondria; Signaling; Acute myocardial infarction; Antivirals; Autophagic degradation; Binding proteins; Inflammasome; Mitochondrial antiviral signaling protein; NLRP3 inflammasome; Ring finger protein 34; Signalling proteins; Tax1-binding protein 1; Proteins
语种	英语
来源期刊	Science Bulletin
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/207630
作者单位	Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, 200032, China; Department of Cardiology, Affiliated Hospital of Nantong University, Jiangsu, 226001, China; Department of Cardiology, Xijing Hospital, Air Force Military Medical University, Xi'an, 710038, China; Department of Pathology, University of Washington, Seattle, WA 98195, United States
推荐引用方式 GB/T 7714	Xu H.,Yu W.,Sun S.,et al. TAX1BP1 protects against myocardial infarction-associated cardiac anomalies through inhibition of inflammasomes in a RNF34/MAVS/NLRP3-dependent manner[J],2021,66(16).
APA	Xu H.,Yu W.,Sun S.,Li C.,Ren J.,&Zhang Y..(2021).TAX1BP1 protects against myocardial infarction-associated cardiac anomalies through inhibition of inflammasomes in a RNF34/MAVS/NLRP3-dependent manner.Science Bulletin,66(16).
MLA	Xu H.,et al."TAX1BP1 protects against myocardial infarction-associated cardiac anomalies through inhibition of inflammasomes in a RNF34/MAVS/NLRP3-dependent manner".Science Bulletin 66.16(2021).