Skip to main content
padlock icon - secure page this page is secure

α7 Nicotinic Acetylcholine Receptor Relieves Angiotensin II–Induced Senescence in Vascular Smooth Muscle Cells by Raising Nicotinamide Adenine Dinucleotide–Dependent SIRT1 Activity

Buy Article:

$52.00 + tax (Refund Policy)

Objective—

α7 nicotinic acetylcholine receptor (α7nAChR) is a subtype of nAChR and has been reported to be involved in hypertension end-organ damage. In this study, we tested the role of α7nAChR in angiotensin II (Ang II)–induced senescence of vascular smooth muscle cells (VSMCs).

Approach and Results—

Expression of α7nAChR was not influenced by Ang II. Ang II induced remarkable senescent phenotypes in rodent and human VSMCs, including increased senescence-associated β-galactosidase activity, phosphorylation of H2A.XSer139, phosphorylation of Chk1Ser317, reduced replication, and downregulation of proliferating cell nuclear antigen. Activation of α7nAChR with a selective agonist PNU-282987 blocked Ang II–induced senescence in cultured VSMCs. Moreover, PNU-282987 treatment attenuated the Ang II infusion–induced VSMC senescence in wild-type but not in α7nAChR−/− mice. PNU-282987 reduced the Ang II–enhanced reactive oxygen species, lipid peroxidation, and the expression of NADPH oxidase 1, NADPH oxidase 4, and p22phox in cultured VSMCs isolated from wild-type but not in α7nAChR−/− mice. Furthermore, PNU-282987 diminished Ang II–induced prosenescence signaling pathways, including p53, acetyl-p53, p21, and p16INK4a. Finally, although α7nAChR activation by PNU-282987 did not affect the Ang II–induced downregulation of sirtuin 1 (SIRT1), it significantly increased intracellular NAD+ levels, and thereby enhanced SIRT1 activity in an AMP-dependent protein kinase–independent manner. Depletion of SIRT1 by knockdown or SIRT1 inhibitor EX527 abrogated the antisenescence effect of α7nAChR against Ang II.

Conclusions—

Our results demonstrate that activation of α7nAChR alleviates Ang II–induced VSMC senescence through promoting NAD+–SIRT1 pathway, suggesting that α7nAChR may be a potential therapeutic target for the treatment of Ang II–associated vascular aging disorders.
No Reference information available - sign in for access.
No Citation information available - sign in for access.
No Supplementary Data.
No Article Media
No Metrics

Keywords: angiotensin II; hypertension; lipid peroxidation; mice; reactive oxygen species

Document Type: Research Article

Publication date: August 1, 2016

  • Access Key
  • Free content
  • Partial Free content
  • New content
  • Open access content
  • Partial Open access content
  • Subscribed content
  • Partial Subscribed content
  • Free trial content
Cookie Policy
X
Cookie Policy
Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more