Zhang Yi-Qiang, Herman Brian
Department of Cellular and Structural Biology, University of Texas HSC at San Antonio, 7703 Floyd Curl Dr., San Antonio, Texas 78249, USA.
J Cell Biochem. 2008 Jun 1;104(3):818-25. doi: 10.1002/jcb.21666.
Apoptosis repressor with a CARD domain (ARC), which has been shown to protect against oxidative stress-induced apoptosis, was initially found to be highly expressed in terminally differentiated tissues like heart and skeletal muscle. Recently, we and others have found that ARC is also expressed at high levels in multiple cancer tissues and cell lines. Here, we compared the regulation of ARC in response to oxidative stress between cancer cells and other types of cells. Similar to cardiomyocyte cell line H9c2 cells, cancer cells with reduced ARC expression were significantly more sensitive to oxidative stress. However, oxidative stress did not down-regulate ARC expression in cancer cells as it did in H9c2 cells. We further found that in H9c2 cells oxidative stress regulates ARC protein expression post-translationally through proteasome-mediated degradation. In cancer cell line HeLa, the majority of ARC exists in phosphorylated state in the absence of oxidative stress, whereas in H9c2 cells only marginal amount of ARC was phosphorylated under similar conditions. Our data suggest that the high level of ARC protein and the constitutive phosphorylation of ARC in cancer cells may play an important role in the protection of cancer cells against oxidative stress.
含CARD结构域的凋亡抑制因子（ARC）最初被发现于心脏和骨骼肌等终末分化组织中高表达，且已证实其具有抵御氧化应激诱导的细胞凋亡的作用。最近，我们和其他研究人员发现ARC在多种癌症组织和细胞系中也有高水平表达。在此，我们比较了癌细胞与其他类型细胞在氧化应激反应中ARC的调控情况。与心肌细胞系H9c2细胞类似，ARC表达降低的癌细胞对氧化应激更为敏感。然而，氧化应激并未像在H9c2细胞中那样下调癌细胞中的ARC表达。我们进一步发现，在H9c2细胞中，氧化应激通过蛋白酶体介导的降解在翻译后水平调控ARC蛋白表达。在癌细胞系HeLa中，在无氧化应激的情况下，大多数ARC以磷酸化状态存在，而在类似条件下H9c2细胞中只有少量ARC被磷酸化。我们的数据表明，癌细胞中ARC蛋白的高水平以及ARC的组成型磷酸化可能在保护癌细胞抵御氧化应激中发挥重要作用。
