Referenced in: none

Automatically associated channels: TRP , TRPV , TRPV1

Title: Nitric oxide induces apoptosis associated with TRPV1 channel-mediated Ca(2+) entry via S-nitrosylation in osteoblasts.

Authors: Leiting Pan, Kun Song, Fen Hu, Wenwu Sun, Imshik Lee

Journal, date & volume: Eur. J. Pharmacol., 2013 Sep 5 , 715, 280-5

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23707350

Abstract
The high-level production of nitric oxide (NO) induced by inflammatory cytokines has been shown to play a key role in the pathogenesis of inflammation-mediated osteoporosis. In the present work, we observed that 1mM of the NO donor sodium nitroprusside (SNP) induced an increase of the cytosolic calcium concentration ([Ca(2+)]c) in osteoblasts, which was completely abolished by applying an extracellular Ca(2+)-free buffer. Further experiments showed that the SNP-induced [Ca(2+)]c increase was specifically blocked by potent antagonists of the transient receptor potential vanilloid subtype 1 (TRPV1) channel: capsazepine, ruthenium red, and La(3+) in Ca(2+)-containing buffer. However, nifedipine, an L-type voltage sensitive Ca(2+)-channel blocker, failed to suppress the [Ca(2+)]c elevation caused by SNP. Additionally, 1mM SNP induced osteoblast apoptosis, which was largely inhibited by the blockers of TRPV1, capsazepine and ruthenium red. Interestingly, our data showed that the SNP-induced [Ca(2+)]c increase was significantly inhibited by N-ethylmaleimide, the blocker of S-nitrosylation modification, instead of inhibitors of the NO-cGMP-PKG pathway. Taken together, our data clearly demonstrated that the NO donor SNP resulted in apoptosis associated with TRPV1 channel-mediated Ca(2+) entry via S-nitrosylation in osteoblasts.