Poly(ADP-ribose) protects vascular smooth muscle cells from oxidative DNA damage.
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.
Vascular Surgery Department of Xuanwu Hospital, Institute of Vascular Surgery, Capital Medical University, Beijing 100053, China.
Chao
C
Zhang
Vascular Surgery Department of Xuanwu Hospital, Institute of Vascular Surgery, Capital Medical University, Beijing 100053, China.
Tao
T
Luo
Vascular Surgery Department of Xuanwu Hospital, Institute of Vascular Surgery, Capital Medical University, Beijing 100053, China.
Shijun
S
Cui
Vascular Surgery Department of Xuanwu Hospital, Institute of Vascular Surgery, Capital Medical University, Beijing 100053, China.
Yongquan
Y
Gu
Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Chunjing
C
Bian
Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Yibin
Y
Chen
Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Xiaochun
X
Yu
Vascular Surgery Department of Xuanwu Hospital, Institute of Vascular Surgery, Capital Medical University, Beijing 100053, China.
Zhonggao
Z
Wang
D000818:Animals; D002478:Cells, Cultured; D004249:DNA Damage; D004260:DNA Repair; D006026:Glycoside Hydrolases / Q000378:metabolism; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology*; D018384:Oxidative Stress / Q000502:physiology; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D011499:Protein Processing, Post-Translational
D011064:Poly Adenosine Diphosphate Ribose; D006026:Glycoside Hydrolases; C022407:poly ADP-ribose glycohydrolase