Rutaecarpine prevents Ang II -induced vascular smooth muscle cell senescence through TRPV1/ SIRT1 pathway
10.3969/j.issn.1001-1978.2022.02.019
- Author:
Yan-Rong YU
1
;
Si-Lu ZHU
1
;
Dan LUO
1
;
Yan-Rong YU
2
;
Xiao-Ying WANG
2
;
Han-Xia WANG
2
;
Xiao-Ying WANG
3
;
Wei-Jie PENG
4
Author Information
1. School of Basic Medicine, Nanchang University, Dept of Physiology
2. School of Pharmacy, Nanchang University, Key i Jib of Basic Pharmacology
3. FuYang People's Hospital, Dept of Pharmacy, Fuyang Anhui
4. Jiangxi Province Key Laboratory of Biomaterials and Biofahrication for Tissue Engineering, Carman Medical University
- Publication Type:Journal Article
- Keywords:
cell senescence;
migration;
Rutaecarpine;
SIRT1;
TRPV1;
vascular smooth muscle cells
- From:
Chinese Pharmacological Bulletin
2022;38(2):261-267
- CountryChina
- Language:Chinese
-
Abstract:
Aim To evaluate the effects of Rutaecarpine(Rut)on the expression of SIRT1 and the senescence of vascular smooth muscle cells(VSMCs)induced by angiotensin Ⅱ.Methods VSMC senescencewas induced by exposure to AngⅡ(1 μmol·L-1)for 72 h.VSMCs were treated with different concentrations of Rut(0.3, 1, 3 μmol·L-1).TRPV1 competitive antagonist CAPZ(10 μmol·L-1)and AMPK inhibitor Compound C(1 μmol·L-1)were used to explore whether TRPV1/AMPK mediated the protective effect of Rut.The quantity of senescent cells were determined by senescence-associated SA-β-Gal staining, and the intracellular ROS level was measured by(DCFH-DA)fluorescent probe.The migration ability of VSMCs was evaluated by Wound-healing assay combined with Transwell assay.The protein level of longevity protein SIRT1 and senescence-related proteins p53, p21 and AMPK phosphorylation level were detected by Western blot.Results Rut significantly inhibited Ang Ⅱ-induced VSMC senescence and ROS production and prevented VSMCs migration.Preprocessing of TRPV1 antagonist CAPZ could abolish the protective effect of Rut.Ang Ⅱ inhibited the expression of longevity protein SIRT1.Rut recovered SIRT1 expression in a dose-dependent manner, while prevented the up-regulation of senescence-related proteins p53 and p21.Ang Ⅱ inhibited AMPK phosphorylation, pre-treatment with Rut restored AMPK phosphorylation level.CAPZ and Compound C eliminated the up-regulating function of Rut on SIRT1 expression.Conclusions Rut up-regulates the expression of SIRT1 and prevents the senescence and migration of VSMCs induced by Angiotensin Ⅱ, which is related to activation of the TRPV1/AMPK signaling pathway.
