1. Academic Validation
  2. Bidirectional regulation role of PARP-1 in high glucose-induced endothelial injury

Bidirectional regulation role of PARP-1 in high glucose-induced endothelial injury

  • Exp Cell Res. 2022 Oct 23;421(2):113400. doi: 10.1016/j.yexcr.2022.113400.
Ying Zhang 1 Wei Wang 2
Affiliations

Affiliations

  • 1 Department of Endocrinology, Shanghai Children's Hospital, Shanghai Jiaotong University, Shanghai, China.
  • 2 Department of Emergency, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address: wangw112039@163.com.
Abstract

Loss of poly (ADP-ribose) polymerase-1 (PARP-1) has been found to slow the progression of diabetes and diabetic angiopathy. In our study, we found bidirectional regulation of PARP-1 in high glucose induced endothelial injury, which promoting repair at the early stage of injury and inhibiting repair at the late stage of injury. To further investigate the mechanism of PARP-1 regulation, we first examined the expression of PARP-1 in aortic tissues and cultured cells at early, middle, and late stages of injury, PARP-1 expression was significantly greater than that of control group. Overexpression of PARP-1 in HUVECs significantly reduced the number of apoptotic cells 12 h after high glucose injury, while reducing the level of Reactive Oxygen Species (ROS)/malondialdehyde (MDA)/inducible nitric oxide synthase (iNOS), increasing the level of endothelial nitric oxide synthase (eNOS); however, when the injury extended to 3 days, the number of Apoptosis in HUVECs overexpressing PARP-1 was significantly higher than that in the injury group, and the level of ROS/MDA/iNOS was significantly higher, while the secretion of eNOS was significantly lower. Similarly, PARP-1 inhibitors aggravate early damage and inhibit late damage. We found that PARP-1 promoted the activation of P53 and P53R2 in endothelial cells after 12 h of injury, and PARP-1 promoted the activation of P53 and caspas3 in endothelial cells after 3 days of injury. Therefore, we suggest that PARP-1 plays a dual regulatory role in promoting repair or aggravating injury.

Keywords

Bidirectional regulative function; Endothelial cells; High glucose; Injury; PARP-1.

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