6-Shogaol Inhibits Oxidative Stress-Induced Rat Vascular Smooth Muscle Cell Apoptosis by Regulating OXR1-p53 Axis

Jing Liu; Bin Li; Wenlian Li; Taowen Pan; Yunpeng Diao; Fangjun Wang

doi:10.3389/fmolb.2022.808162

6-Shogaol Inhibits Oxidative Stress-Induced Rat Vascular Smooth Muscle Cell Apoptosis by Regulating OXR1-p53 Axis

Front Mol Biosci. 2022 Jan 31:9:808162. doi: 10.3389/fmolb.2022.808162. eCollection 2022.

Authors

Jing Liu^{1

2

3}, Bin Li^{1

3}, Wenlian Li¹, Taowen Pan^{1

3}, Yunpeng Diao^{1

3}, Fangjun Wang²

Affiliations

¹ College of Pharmacy, College of Integrative Medicine, Dalian Medical University, Dalian, China.
² Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
³ Dalian Anti-Infective Traditional Chinese Medicine Development Engineering Technology Research Center, Dalian, China.

Abstract

Apoptosis of vascular smooth muscle cells (VSMCs) is closely related to the pathogenesis of cardiovascular diseases, and oxidative stress is an important cause of VSMCs' death. Inhibiting VSMCs apoptosis is an effective preventive strategy in slowing down the development of cardiovascular disease, especially for atherosclerosis. In this study, we found that oxidation resistance protein 1 (OXR1), a crucial participator for responding to oxidative stress, could modulate the expression of p53, the key regulator of cell apoptosis. Our results revealed that oxidative stress promoted VSMCs apoptosis by overexpression of the OXR1-p53 axis, and 6-shogaol (6S), a major biologically active compound in ginger, could effectively attenuate cell death by preventing the upregulated expression of the OXR1-p53 axis. Quantitative proteomics analysis revealed that the degradation of p53 mediated by OXR1 might be related to the enhanced assembly of SCF ubiquitin ligase complexes, which is reported to closely relate to the modification of ubiquitination or neddylation and subsequent degradation of p53.

Keywords: 6-shogaol (PubChem CID: 5281794); OXR1; apoptosis; oxidative stress; p53; vascular smooth muscle cell.

Grants and funding

This work was supported by the National Natural Science Foundation of China (81702995), the Natural Science Foundation of Liaoning Province (2020-MS-246), and the Scientific Research Funding Project of the Liaoning Provincial Department of Education (LZ2020016). The open-access publication fees were from JL’s lab.