title: TRPC5 channel modulates endothelial cells senescence.
abstract: 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 β-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.
authors.affiliation: Ethnic Drug Screening & Pharmacology Center, Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, Yunnan Minzu University, Kunming 650500, PR China.
authors.forename: Zhengtao
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, Third Affiliated Hospital of Kunming Medical University, Kunming 650118, PR China.
authors.forename: Gang
authors.initials: G
authors.lastname: Guo
authors.affiliation: Ethnic Drug Screening & Pharmacology Center, Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, Yunnan Minzu University, Kunming 650500, PR China.
authors.forename: Hongrui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Ethnic Drug Screening & Pharmacology Center, Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, Yunnan Minzu University, Kunming 650500, PR China.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Si
authors.affiliation: Ethnic Drug Screening & Pharmacology Center, Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, Yunnan Minzu University, Kunming 650500, PR China.
authors.forename: Guoli
authors.initials: G
authors.lastname: Zhou
authors.affiliation: Ethnic Drug Screening & Pharmacology Center, Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, Yunnan Minzu University, Kunming 650500, PR China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Ethnic Drug Screening & Pharmacology Center, Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, Yunnan Minzu University, Kunming 650500, PR China.
authors.forename: Sujuan
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Yunnan University of TCM, Kunming 650500, PR China. Electronic address: 1647029626@qq.com.
authors.forename: Rong
authors.initials: R
authors.lastname: Dai
authors.affiliation: Ethnic Drug Screening & Pharmacology Center, Key Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, Yunnan Minzu University, Kunming 650500, PR China; Beijing Key Laboratory of Drug Target Research and Drug Screen, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, PR China. Electronic address: yangynni@163.com.
authors.forename: Cui
authors.initials: C
authors.lastname: Yang
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology; D016922:Cellular Senescence; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D055786:Gene Knockout Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D050052:TRPC Cation Channels / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D050052:TRPC Cation Channels; C112021:Trpc5 protein, mouse
keywords: Endothelial senescence; Oxidative stress; TRPC5; Vascular aging