UCP2 overexpression activates SIRT3 to regulate oxidative stress and mitochondrial dynamics induced by myocardial injury

IF 3.8 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Archives of biochemistry and biophysics Pub Date : 2024-01-30 DOI:10.1016/j.abb.2024.109918

Zhengguang Geng , Wenbo Chen , Qinju Lu , Bao Fu , Xiaoyun Fu

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引用次数: 0

Abstract

Objective

Our previous study found that overexpression of uncoupling protein-2 (UCP2) had a protective effect on lipopolysaccharide (LPS)-induced sepsis cardiomyocytes. The aim of this study was to explore the effect and mechanism of uncoupling protein-2 (UCP2) on myocardial ischemia-reperfusion injury.

Methods

In this study, we established hypoxia-reoxygenation (HR) injury model in rats and isolated cardiomyocytes of newborn rats. We also carried out following methods which include virus transfection technology, cell counting Kit-8 (CCK8), flow cytometry, enzyme linked immunosorbent assay (ELISA), Western blot (WB), quantitative reverse transcription PCR (RT qPCR), transmission electron microscopy, fluorescence colocalization and immunoprecipitation.

Main results

The results of this study showed that hypoxia-reoxygenation treatment in cardiomyocytes increased UCP2, myocardial enzyme and myocardial apoptosis and weakened cardiomyocyte viability. We observed increased cardiomyocyte viability and mitochondrial membrane potential, decreased myocardial enzyme and myocardial apoptosis, Inhibition of oxidative stress when UCP2 was overexpressed in cardiomyocytes. It also can Increase ATP and stabilize mitochondrial dynamics. Further studies founded that Sirtuin-3(SIRT3) changed with the expression of UCP2, which was confirmed by fluorescence co-localization and immunoprecipitation.

Conclusions

Our findings revealed that UCP2 and SIRT3 were important targets of anti-myocardial injury by inhibiting cellular oxidative stress and stabilizing mitochondrial dynamics.

Abstract Image

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UCP2 过表达可激活 SIRT3，从而调节心肌损伤诱发的氧化应激和线粒体动态变化

目的我们之前的研究发现，过表达解偶联蛋白-2（UCP2）对脂多糖（LPS）诱导的脓毒症心肌细胞有保护作用。本研究旨在探讨解偶联蛋白-2（UCP2）对心肌缺血再灌注损伤的影响及其机制。并采用病毒转染技术、细胞计数试剂盒-8（CCK8）、流式细胞术、酶联免疫吸附试验（ELISA）、Western blot（WB）、反转录定量 PCR（RT qPCR）、透射电子显微镜、荧光共聚焦和免疫沉淀等方法进行研究。主要结果本研究结果表明，低氧-复氧处理会增加心肌细胞中的 UCP2、心肌酶和心肌细胞凋亡，并削弱心肌细胞的活力。当 UCP2 在心肌细胞中过表达时，我们观察到心肌细胞活力和线粒体膜电位增加，心肌酶和心肌凋亡减少，氧化应激抑制。它还能增加 ATP 和稳定线粒体动力学。进一步的研究发现，Sirtuin-3（SIRT3）会随着 UCP2 的表达而发生变化，这一点通过荧光共定位和免疫沉淀得到了证实。

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来源期刊

Archives of biochemistry and biophysics 生物-生化与分子生物学

CiteScore

7.40

自引率

0.00%

发文量

245

审稿时长

26 days

期刊介绍： Archives of Biochemistry and Biophysics publishes quality original articles and reviews in the developing areas of biochemistry and biophysics. Research Areas Include: • Enzyme and protein structure, function, regulation. Folding, turnover, and post-translational processing • Biological oxidations, free radical reactions, redox signaling, oxygenases, P450 reactions • Signal transduction, receptors, membrane transport, intracellular signals. Cellular and integrated metabolism.