Thymosin beta 4 protects cardiomyocytes from oxidative stress by targeting anti-oxidative enzymes and anti-apoptotic genes.
Thymosin beta 4 protects cardiomyocytes from oxidative stress by targeting anti-oxidative enzymes and anti-apoptotic genes.
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DOI：
10.1371/journal.pone.0042586
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Gupta S
中科院分区：
文献类型：
--
作者：
Wei C;Kumar S;Kim IK;Gupta S
胸腺素β-4（Tβ4）是一种普遍存在的蛋白质，具有与细胞增殖和分化相关的许多特性，可促进伤口愈合并调节炎症介质。Tβ4调节氧化应激下心脏保护作用的机制尚不清楚。本研究旨在探讨Tβ4对H2 O2所致心肌损伤的保护机制。将有或没有Tβ4预处理的大鼠新生心肌细胞暴露于H2 O2，并通过定量实时PCR和蛋白质印迹法评估抗氧化、凋亡和抗炎基因的表达。使用荧光显微镜和荧光测定法通过DCF-DA估计ROS水平。选择抗氧化，抗炎和抗凋亡基因沉默的siRNA转染在新生心肌细胞和Tβ4对H2 O2诱导的心脏损伤的影响进行了评估。Tβ4预处理可降低H2 O2诱导的心肌细胞内ROS水平。Tβ4预处理还导致心肌细胞抗凋亡蛋白表达增加，Bax/BCl 2比值降低。Tβ4预处理可在转录和翻译水平上刺激心肌细胞抗氧化酶铜/锌SOD和过氧化氢酶的表达。Tβ4处理导致抗凋亡和抗炎基因的表达增加。Cu/Zn SOD和过氧化氢酶基因的沉默导致心肌细胞的凋亡，而Tβ4的治疗可以阻止这种凋亡。这是第一份证明Tβ4对心肌细胞的作用及其选择性上调新生心肌细胞中抗氧化酶、抗炎基因和抗凋亡酶的能力，从而防止细胞死亡，从而保护心肌的报告。Tβ4治疗导致氧化应激和氧化应激下的心肌炎症减少。
Thymosin beta-4 (Tβ4) is a ubiquitous protein with many properties relating to cell proliferation and differentiation that promotes wound healing and modulates inflammatory mediators. The mechanism by which Tβ4 modulates cardiac protection under oxidative stress is not known. The purpose of this study is to dissect the cardioprotective mechanism of Tβ4 on H2O2 induced cardiac damage. Rat neonatal cardiomyocytes with or without Tβ4 pretreatment were exposed to H2O2 and expression of antioxidant, apoptotic, and anti-inflammatory genes was evaluated by quantitative real-time PCR and western blotting. ROS levels were estimated by DCF-DA using fluorescent microscopy and fluorimetry. Selected antioxidant, anti-inflammatory and antiapoptotic genes were silenced by siRNA transfections in neonatal cardiomyocytes and effect of Tβ4 on H2O2-induced cardiac damage was evaluated. Pre-treatment of Tβ4 resulted in reduction of the intracellular ROS levels induced by H2O2 in cardiomyocytes. Tβ4 pretreatment also resulted in an increase in the expression of antiapoptotic proteins and reduction of Bax/BCl2 ratio in the cardiomyocytes. Pretreatment with Tβ4 resulted in stimulating the expression of antioxidant enzymes copper/zinc SOD and catalase in cardiomyocytes at both transcription and translation levels. Tβ4 treatment resulted in the increased expression of anti-apoptotic and anti-inflammatory genes. Silencing of Cu/Zn SOD and catalase gene resulted in apoptotic cell death in the cardiomyocytes which was prevented by treatment with Tβ4. This is the first report that demonstrates the effect of Tβ4 on cardiomyocytes and its capability to selectively upregulate anti-oxidative enzymes, anti-inflammatory genes, and antiapoptotic enzymes in the neonatal cardiomyocytes thus preventing cell death thereby protecting the myocardium. Tβ4 treatment resulted in decreased oxidative stress and inflammation in the myocardium under oxidative stress.
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DOI：
10.1042/bj20081386
发表时间：
2009-01-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Murphy MP
通讯作者：
Murphy MP
DOI：
10.1152/ajpheart.00379.2005
发表时间：
2006-02-01
影响因子：
4.8
作者：
Higuchi, Y;Chan, TO;Feldman, AM
通讯作者：
Feldman, AM
影响因子：
20.1
作者：
Ide, T;Tsutsui, H;Takeshita, A
通讯作者：
Takeshita, A
影响因子：
64.8
作者：
Baines, CP;Kaiser, RA;Molkentin, JD
通讯作者：
Molkentin, JD
影响因子：
5
作者：
Chen, ZY;Siu, B;Chua, BHL
通讯作者：
Chua, BHL