Increased temperature and protein oxidation lead to HSP72 mRNA and protein accumulation in the in vivo exercised rat heart.
Increased temperature and protein oxidation lead to HSP72 mRNA and protein accumulation in the in vivo exercised rat heart.
复制标题
温度升高和蛋白质氧化导致 HSP72 mRNA 和蛋白质在体内运动的大鼠心脏中积累。
DOI：
10.1113/expphysiol.2008.044685
复制
发表时间：
2009
影响因子：
2.7
通讯作者：
Powers,ScottK
中科院分区：
文献类型：
--
作者：
Staib,JessicaL;Tümer,Nihal;Powers,ScottK
心肌热休克蛋白72（HSP 72）的表达，由其转录因子，热休克因子1（HSF 1）介导，运动后增加。然而，在整个动物中，控制运动诱导的HSF1激活和Hsp72基因表达的上游刺激仍然不清楚。运动引起的体温升高可能会促进心肌自由基的产生，导致蛋白质氧化。运动时心肌蛋白质氧化可能是促进核HSF 1迁移和激活Hsp 72表达的重要信号。因此，这些实验验证了这样一个假设，即预防运动诱导的体温升高会减弱心脏蛋白氧化，减少HSF 1活化并降低体内HSP 72表达。为了验证这一假设，通过在寒冷（4°C）或温暖环境条件（22°C）下锻炼雄性大鼠来操纵体内运动诱导的体温变化。温暖的运动增加了体温（+3°C）和心肌蛋白氧化，而这些变化被冷运动减弱。有趣的是，在这两种情况下，运动并没有显着增加心肌核定位磷酸化HSF1。尽管如此，与冷运动动物相比，温暖运动使左心室HSP72 mRNA增加了9倍，心肌HSP72蛋白水平增加了3倍。总的来说，这些数据表明，体温升高和心肌蛋白氧化促进运动诱导的心脏HSP 72 mRNA表达和体内运动后的蛋白积累。然而，这些结果表明，运动诱导的心肌HSP72蛋白积聚不是核定位的磷酸化HSF1的结果，表明其他转录或转录后调节机制参与运动诱导的HSP72表达。
Expression of myocardial heat shock protein 72 (HSP72), mediated by its transcription factor, heat shock factor 1 (HSF1), increases following exercise. However, the upstream stimuli governing exercise‐induced HSF1 activation and subsequentHsp72gene expression in the whole animal remain unclear. Exercise‐induced increases in body temperature may promote myocardial radical production, leading to protein oxidation. Conceivably, myocardial protein oxidation during exercise may serve as an important signal to promote nuclear HSF1 migration and activation ofHsp72expression. Therefore, these experiments tested the hypothesis that prevention of exercise‐induced increases in body temperature attenuates cardiac protein oxidation, diminishes HSF1 activation and decreases HSP72 expressionin vivo. To test this hypothesis,in vivoexercise‐induced changes in body temperature were manipulated by exercising male rats in either cold (4°C) or warm ambient conditions (22°C). Warm exercise increased both body temperature (+3°C) and myocardial protein oxidation, whereas these changes were attenuated by cold exercise. Interestingly, exercise in both conditions did not significantly increase myocardial nuclear localized phosphorylated HSF1. Nonetheless, warm exercise elevated left‐ventricular HSP72 mRNA by ninefold and increased myocardial HSP72 protein levels by threefold compared with cold‐exercised animals. Collectively, these data indicate that elevated body temperature and myocardial protein oxidation promoted exercise‐induced cardiac HSP72 mRNA expression and protein accumulation followingin vivoexercise. However, these results suggest that exercise‐induced myocardial HSP72 protein accumulation is not a result of nuclear‐localized, phosphorylated HSF1, indicating that other transcriptional or post‐transcriptional regulatory mechanisms are involved in exercise‐induced HSP72 expression.