Poly(ADP-ribose) protects vascular smooth muscle cells from oxidative DNA damage.
Poly(ADP-ribose) protects vascular smooth muscle cells from oxidative DNA damage.
复制标题
聚 (ADP-核糖) 保护血管平滑肌细胞免受氧化 DNA 损伤。
DOI：
10.5483/bmbrep.2015.48.6.012
复制
发表时间：
2015-06
期刊：
影响因子：
3.8
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Zhang C;Luo T;Cui S;Gu Y;Bian C;Chen Y;Yu X;Wang Z
血管平滑肌细胞 (VSMC) 在动脉粥样硬化（一种普遍存在的心血管疾病）过程中死亡。最近的研究表明，VSMC 发生氧化损伤并诱发动脉粥样硬化。在这里，我们分析了 VSMC 中的氧化损伤修复，发现 VSMC 对氧化损伤高度敏感。进一步分析表明，VSMC 中的氧化损伤修复受到低水平的多聚（ADP-核糖基）化（PARylation）的抑制，这是氧化损伤修复中关键的翻译后修饰。 PARylation 水平低并不是由于缺乏 PARP-1（氧化损伤激活的主要聚（ADP-核糖）聚合酶）引起的。相反，VSMC 中聚（ADP-核糖）糖水解酶、PARG（水解聚（ADP-核糖）的酶）的表达显着高于对照细胞。使用 PARG 抑制剂抑制 PARG 活性可促进氧化损伤诱导的 PARylation 以及 DNA 损伤修复。因此，我们的研究证明了氧化损伤诱导 VSMC 死亡的新分子机制。这项研究还确定了使用 PARG 抑制剂作为动脉粥样硬化的潜在治疗方法。 [2015 年 BMB 报告； 48（6）：354-359]
Vascular smooth muscle cells (VSMCs) undergo death during atherosclerosis, a widespread cardiovascular disease. Recent studies suggest that oxidative damage occurs in VSMCs and induces atherosclerosis. Here, we analyzed oxidative damage repair in VSMCs and found that VSMCs are hypersensitive to oxidative damage. Further analysis showed that oxidative damage repair in VSMCs is suppressed by a low level of poly (ADP-ribosyl)ation (PARylation), a key post-translational modification in oxidative damage repair. The low level of PARylation is not caused by the lack of PARP-1, the major poly(ADP-ribose) polymerase activated by oxidative damage. Instead, the expression of poly(ADP-ribose) glycohydrolase, PARG, the enzyme hydrolyzing poly(ADP-ribose), is significantly higher in VSMCs than that in the control cells. Using PARG inhibitor to suppress PARG activity facilitates oxidative damage-induced PARylation as well as DNA damage repair. Thus, our study demonstrates a novel molecular mechanism for oxidative damage-induced VSMCs death. This study also identifies the use of PARG inhibitors as a potential treatment for atherosclerosis. [BMB Reports 2015; 48(6): 354-359]