Ichiki Toshihiro, Miyazaki Ryohei, Kamiharaguchi Aya, Hashimoto Toru, Matsuura Hirohide, Kitamoto Shiro, Tokunou Tomotake, Sunagawa Kenji
Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Japan.
Regul Pept. 2012 Aug 20;177(1-3):35-9. doi: 10.1016/j.regpep.2012.04.005. Epub 2012 May 2.
Resveratrol (3,5,4'-trihydroxystilbene), a polyphenol abundant in red wine, is known to extend the life span of diverse species. On the contrary, it was reported that angiotensin (Ang) II enhances senescence of vascular smooth muscle cells (VSMCs). We, therefore, examined whether resveratrol attenuates Ang II-induced senescence of VSMC. Senescence-associated β-galactosidase (SA β-gal) assay showed that Ang II induced senescence of VSMC. The Ang II-induced senescence was inhibited by losartan, an Ang II type 1 receptor (AT1R) antagonist but not by PD123319, Ang II type 2 receptor antagonist, indicating that AT1R is responsible for the induction of senescence. Resveratrol suppressed Ang II-induced senescence of VSMC in a dose-dependent manner. In addition, resveratrol suppressed Ang II-induced induction of p53 and its downstream target gene p21, both of which play an important role in the induction of senescence. Resveratrol suppressed senescence of VSMC possibly through inhibition of AT1R-dependent induction of p53/p21. Suppression of p53 induction may be involved in the longevity by resveratrol.
白藜芦醇（3,5,4'-三羟基茋）是一种在红酒中大量存在的多酚，已知它能延长多种物种的寿命。相反，有报道称血管紧张素（Ang）II会增强血管平滑肌细胞（VSMC）的衰老。因此，我们研究了白藜芦醇是否能减轻Ang II诱导的VSMC衰老。衰老相关β-半乳糖苷酶（SA β-gal）检测表明，Ang II可诱导VSMC衰老。Ang II诱导的衰老可被氯沙坦（一种Ang II 1型受体（AT1R）拮抗剂）抑制，但不能被PD123319（Ang II 2型受体拮抗剂）抑制，这表明AT1R负责诱导衰老。白藜芦醇以剂量依赖的方式抑制Ang II诱导的VSMC衰老。此外，白藜芦醇抑制Ang II诱导的p53及其下游靶基因p21的表达，这两者在衰老诱导中都起重要作用。白藜芦醇可能通过抑制AT1R依赖的p53/p21诱导来抑制VSMC衰老。抑制p53诱导可能与白藜芦醇的长寿作用有关。
