Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada N2L3G1.
Biochem Biophys Res Commun. 2010 Jan 15;391(3):1437-42. doi: 10.1016/j.bbrc.2009.12.084. Epub 2009 Dec 21.
Apoptosis repressor with caspase recruitment domain (ARC) is a unique anti-apoptotic protein with a distinct tissue distribution. In addition, unlike most anti-apoptotic proteins which act on one pathway, ARC can inhibit apoptosis mediated by both the death-receptor and mitochondrial signaling pathways. In this study, we confirm previous reports showing high levels of ARC protein in rat heart and skeletal muscle, but demonstrate for the first time that ARC is also expressed in rat aorta. Immunoblot analysis on endothelium-denuded aorta as well as immunohistochemical analysis on intact aorta demonstrated that ARC was highly expressed in smooth muscle. Immunoblot analysis also found that ARC protein was severely downregulated in skeletal muscle (-82%; P<0.001), heart (-80%; P<0.001), and aorta (-71%; P<0.001) of spontaneously hypertensive rats (SHR) compared to normotensive Wistar-Kyoto (WKY) rats. Decreased ARC levels were also confirmed in tissues of hypertensive animals by immunohistochemical analysis. Collectively, this data suggests that ARC protein is expressed in vascular smooth muscle and is significantly reduced in several target tissues during hypertension.
凋亡抑制因子 with caspase recruitment domain（ARC）是一种独特的抗凋亡蛋白，具有独特的组织分布。此外，与大多数作用于单一途径的抗凋亡蛋白不同，ARC 可以抑制死亡受体和线粒体信号通路介导的凋亡。在这项研究中，我们证实了之前的报道，即 ARC 蛋白在大鼠心脏和骨骼肌中水平较高，但首次证明 ARC 也在大鼠主动脉中表达。对去内皮主动脉进行免疫印迹分析以及对完整主动脉进行免疫组织化学分析表明，ARC 在平滑肌中高度表达。免疫印迹分析还发现，与正常血压的 Wistar-Kyoto（WKY）大鼠相比，自发性高血压大鼠（SHR）的骨骼肌（-82%；P<0.001）、心脏（-80%；P<0.001）和主动脉（-71%；P<0.001）中的 ARC 蛋白水平严重下调。免疫组织化学分析也证实了高血压动物组织中 ARC 水平降低。总的来说，这些数据表明 ARC 蛋白在血管平滑肌中表达，并在高血压期间在几个靶组织中显著减少。
