Quadrilatero Joe, Rush James W E
Department of Kinesiology, University of Waterloo, 200 University Avenue West, Waterloo, Ont., Canada.
Biochem Biophys Res Commun. 2008 Mar 28;368(1):168-74. doi: 10.1016/j.bbrc.2008.01.067. Epub 2008 Jan 22.
In this report, we demonstrate that soleus muscle of spontaneously hypertensive rats (SHR) had significantly lower protein levels of apoptosis repressor with caspase recruitment domain (ARC) and X-linked inhibitor of apoptosis protein (XIAP) as well as significantly higher protein levels of second mitochondria-derived activator of caspase (Smac) and procaspase-8 compared to normotensive Wistar-Kyoto (WKY) rats. In addition, soleus muscle from hypertensive rats had significantly increased caspase-8 proteolytic enzyme activity as well as significantly elevated reactive oxygen species (ROS) generation and higher hydrogen peroxide (H(2)O(2)) content. There was no change in the protein levels of the antioxidant enzymes, catalase, copper-zinc superoxide dismutase (CuZnSOD), and manganese superoxide dismutase (MnSOD). Interestingly, ARC protein migrated at approximately 32kDa in SHR but at 30kDa in WKY rat muscle; possibly indicating a post-translational modification. These results demonstrate that soleus muscle of hypertensive rats display a pro-apoptotic phenotype and augmented ROS generation.
在本报告中，我们证明，与正常血压的Wistar-Kyoto（WKY）大鼠相比，自发性高血压大鼠（SHR）的比目鱼肌中，含半胱天冬酶募集结构域的凋亡抑制蛋白（ARC）和X连锁凋亡抑制蛋白（XIAP）的蛋白水平显著降低，而第二线粒体衍生的半胱天冬酶激活剂（Smac）和半胱天冬酶原-8的蛋白水平显著升高。此外，高血压大鼠的比目鱼肌中，半胱天冬酶-8蛋白水解酶活性显著增加，活性氧（ROS）生成显著升高，过氧化氢（H₂O₂）含量更高。抗氧化酶过氧化氢酶、铜锌超氧化物歧化酶（CuZnSOD）和锰超氧化物歧化酶（MnSOD）的蛋白水平没有变化。有趣的是，ARC蛋白在SHR中迁移至约32kDa，但在WKY大鼠肌肉中迁移至30kDa；这可能表明存在翻译后修饰。这些结果表明，高血压大鼠的比目鱼肌表现出促凋亡表型和增强的ROS生成。
