PMID- 28237267
OWN - NLM
STAT- MEDLINE
DCOM- 20170502
LR  - 20171116
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 802
DP  - 2017 May 5
TI  - TRPC5 channel modulates endothelial cells senescence.
PG  - 27-35
LID - S0014-2999(17)30114-0 [pii]
LID - 10.1016/j.ejphar.2017.02.037 [doi]
AB  - As a Ca(2+)-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.
CI  - Copyright (c) 2017 Elsevier B.V. All rights reserved.
FAU - Li, Zhengtao
AU  - Li Z
AD  - 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.
FAU - Guo, Gang
AU  - Guo G
AD  - Department of Thoracic Surgery, Third Affiliated Hospital of Kunming Medical 
      University, Kunming 650118, PR China.
FAU - Wang, Hongrui
AU  - Wang H
AD  - 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.
FAU - Si, Xiaoqin
AU  - Si X
AD  - 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.
FAU - Zhou, Guoli
AU  - Zhou G
AD  - 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.
FAU - Xiong, Yong
AU  - Xiong Y
AD  - 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.
FAU - Li, Sujuan
AU  - Li S
AD  - 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.
FAU - Dai, Rong
AU  - Dai R
AD  - Department of Pharmacology, Yunnan University of TCM, Kunming 650500, PR China. 
      Electronic address: 1647029626@qq.com.
FAU - Yang, Cui
AU  - Yang C
AD  - 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.
LA  - eng
PT  - Journal Article
DEP - 20170222
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (TRPC Cation Channels)
RN  - 0 (Trpc5 protein, mouse)
SB  - IM
MH  - Aging/metabolism
MH  - Animals
MH  - Aorta, Thoracic/physiology
MH  - *Cellular Senescence
MH  - Endothelial Cells/*cytology/metabolism
MH  - Gene Knockout Techniques
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Oxidative Stress
MH  - TRPC Cation Channels/deficiency/genetics/*metabolism
OTO - NOTNLM
OT  - Endothelial senescence
OT  - Oxidative stress
OT  - TRPC5
OT  - Vascular aging
EDAT- 2017/02/27 06:00
MHDA- 2017/05/04 06:00
CRDT- 2017/02/27 06:00
PHST- 2016/07/20 00:00 [received]
PHST- 2017/02/16 00:00 [revised]
PHST- 2017/02/21 00:00 [accepted]
PHST- 2017/02/27 06:00 [pubmed]
PHST- 2017/05/04 06:00 [medline]
PHST- 2017/02/27 06:00 [entrez]
AID - S0014-2999(17)30114-0 [pii]
AID - 10.1016/j.ejphar.2017.02.037 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2017 May 5;802:27-35. doi: 10.1016/j.ejphar.2017.02.037. Epub 
      2017 Feb 22.