As a Ca2+-permeable cationic channel, canonical transient receptor potential 5 channel (TRPC5) has been known to be involved in various functions of cells. Although TRPC5 is abundantly expressed in vascular endothelium, it remains unknown whether TRPC5 plays a role in regulating endothelial senescence. In the present study, we investigated the involvement of TRPC5 in the senescence of mouse aortic endothelial cells (MAECs). Meanwhile, the regulatory role of TRPC5 in the endothelial dysfunction in aged mice was also studied. Results showed that the endothelium-dependent relaxations were significantly promoted but the endothelium-dependent contractions were markedly attenuated in aortic rings from aged mice with TRPC5 gene knocked out compared with those from aged C57BL/6J mice. Meanwhile, the nuclear telomerase activity and nitric oxide generation were notably enhanced but the reactive oxygen species production was significantly inhibited in aged mice or in hydrogen peroxide-induced senescent MAECs lacking the TRPC5 gene. In addition, by performing the senescence-associated beta-galactosidase staining the oxidative stress-induced premature senescence was markedly depressed in MAECs with TRPC5 gene deficient. Expressions of endothelial nitric oxide synthase and silent information regulator protein 1 (SIRT1) were significantly up-regulated but those of P53 and P21 were markedly down-regulated both in aged mice and in hydrogen peroxide-treated MAECs in the absence of the TRPC5 gene. These results of our study uncover novel functions of TRPC5 in regulating vascular aging.
[1]Yunnan Minzu Univ, Ethn Drug Screening & Pharmacol Ctr, Key Lab Chem Ethn Med Resources, State Ethn Affairs Commiss, Kunming 650500, Peoples R China.
[2]Yunnan Minzu Univ, Minist Educ, Kunming 650500, Peoples R China.
[3]Kunming Med Univ, Affiliated Hosp 3, Dept Thorac Surg, Kunming 650118, Peoples R China.
[4]Yunnan Univ TCM, Dept Pharmacol, Kunming 650500, Peoples R China.
[5]Chinese Acad Med Sci, Inst Mat Med, Beijing Key Lab Drug Target Res & Drug Screen, Beijing 100050, Peoples R China.
[6]Peking Union Med Coll, Beijing 100050, Peoples R China.
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