TRAF3IP3 Blocks Mitophagy to Exacerbate Myocardial Injury Induced by Ischemia-Reperfusion.

IF 3.4 3区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Cardiovascular Toxicology Pub Date : 2024-11-01 Epub Date: 2024-09-06 DOI:10.1007/s12012-024-09916-8

Zhongcheng Wei, Juan Liu, Hailang Liu, Aixia Jiang

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Abstract

To uncover the possible role of TRAF3IP3 in the progression of myocardial infarction (MI), clarify its role in mitophagy and mitochondrial function, and explore the underlying mechanism. GEO chip analysis, RT-qPCR, and LDH release assay were used to detect the expression of TRAF3IP3 in tissues and cells and its effects on cell damage. Immunostaining and ATP product assays were performed to examine the effects of TRAF3IP3 on mitochondrial function. Co-IP, CHX assays, Immunoblot and Immunostaining assays were conducted to determine the effects of TRAF3IP3 on mitophagy. TRAF3IP3 was highly expressed in IR rats and HR-induced H9C2 cells. TRAF3IP3 knockdown can alleviate H/R-induced H9C2 cell damage. In addition, TRAF3IP3 knockdown can induce mitophagy, thus enhancing mitochondrial function. We further revealed that TRAF3IP3 can promote the degradation of NEDD4 protein. Moreover, TRAF3IP3 knockdown suppressed myocardial injury in I/R rats. TRAF3IP3 blocks mitophagy to exacerbate myocardial injury induced by I/R via mediating NEDD4 expression.

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TRAF3IP3阻碍丝裂细胞吞噬，加剧缺血再灌注引起的心肌损伤

揭示TRAF3IP3在心肌梗死（MI）进展中的可能作用，阐明其在有丝分裂和线粒体功能中的作用，并探索其潜在机制。研究人员利用 GEO 芯片分析、RT-qPCR 和 LDH 释放试验检测 TRAF3IP3 在组织和细胞中的表达及其对细胞损伤的影响。通过免疫染色和 ATP 产物检测来研究 TRAF3IP3 对线粒体功能的影响。为了确定 TRAF3IP3 对有丝分裂的影响，还进行了 Co-IP、CHX 试验、免疫印迹和免疫染色试验。TRAF3IP3在IR大鼠和HR诱导的H9C2细胞中高表达。敲除 TRAF3IP3 可减轻 H/R 诱导的 H9C2 细胞损伤。此外，TRAF3IP3敲除可诱导有丝分裂，从而增强线粒体功能。我们进一步发现，TRAF3IP3 能促进 NEDD4 蛋白的降解。此外，TRAF3IP3敲除抑制了I/R大鼠的心肌损伤。TRAF3IP3通过介导NEDD4的表达阻断了有丝分裂，从而加剧了I/R诱导的心肌损伤。

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来源期刊

Cardiovascular Toxicology 医学-毒理学

CiteScore

6.60

自引率

3.10%

发文量

审稿时长

>12 weeks

期刊介绍： Cardiovascular Toxicology is the only journal dedicated to publishing contemporary issues, timely reviews, and experimental and clinical data on toxicological aspects of cardiovascular disease. CT publishes papers that will elucidate the effects, molecular mechanisms, and signaling pathways of environmental toxicants on the cardiovascular system. Also covered are the detrimental effects of new cardiovascular drugs, and cardiovascular effects of non-cardiovascular drugs, anti-cancer chemotherapy, and gene therapy. In addition, Cardiovascular Toxicology reports safety and toxicological data on new cardiovascular and non-cardiovascular drugs.