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Upregulation of sestrin-2 expression protects against endothelial toxicity of angiotensin II
| Content Provider | Paperity |
|---|---|
| Author | Jiewen, Li Li, Feng Yong, Yuan Liting, Zhang Fei, Li Jianting, Dong Yi, Lao Xuansheng, Huang |
| Abstract | Sestrin-2 (SESN2) is involved in the cellular response to different stress conditions. However, the function of SESN2 in the cardiovascular system remains unknown. In the present study, we tested whether SESN2 has a beneficial effect on vascular endothelial damage induced by angiotensin II (AngII). Firstly, we found that AngII induces expression of SESN2 in human umbilical vein endothelial cells (HUVECs) in a time-dependent and dose-dependent manner. We also found that knockdown of SESN2 using small RNA interference promotes cellular toxicity of AngII, as well as a reduction in cell viability, exacerbation of oxidative stress, and stimulation of apoptosis. In addition, our results show that the c-Jun NH (2)-terminal kinase (JNK)/c-Jun pathway is activated by AngII. Inhibiting the activity of the JNK pathway abolishes the increase in SESN2 induced by AngII. Importantly, overexpression of c-Jun promotes luciferase activity of the SESN2 promoter. These findings suggest that the inductive effect of SESN2 is mediated by the JNK/c-Jun pathway. Our results indicate that the induction of SESN2 acts as a compensatory response to AngII for survival, implying that stimulating expression of SESN2 might be an effective pharmacological target for the treatment of AngII-associated cardiovascular diseases. |
| Starting Page | 147 |
| Ending Page | 156 |
| File Format | HTM / HTML |
| ISSN | 07422091 |
| DOI | 10.1007/s10565-014-9276-3 |
| Issue Number | 3 |
| Journal | Cell Biology and Toxicology |
| Volume Number | 30 |
| e-ISSN | 15736822 |
| Language | English |
| Publisher | Springer Netherlands |
| Publisher Date | 2014-06-01 |
| Access Restriction | Open |
| Subject Keyword | Oxidative stress Sestrin-2 Angiotensin ii Jnk |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Health, Toxicology and Mutagenesis Toxicology |
