title: Nitric oxide induces apoptosis associated with TRPV1 channel-mediated Ca(2+) entry via S-nitrosylation in osteoblasts.
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.
authors.affiliation: The Key Laboratory of Weak-Light Nonlinear Photonics, Ministry of Education, TEDA Applied Physics School and School of Physics, Nankai University, Tianjin, China.
authors.forename: Leiting
authors.initials: L
authors.lastname: Pan
authors.forename: Kun
authors.initials: K
authors.lastname: Song
authors.forename: Fen
authors.initials: F
authors.lastname: Hu
authors.forename: Wenwu
authors.initials: W
authors.lastname: Sun
authors.forename: Imshik
authors.initials: I
authors.lastname: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000378:metabolism* / Q000494:pharmacology*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D026403:S-Nitrosothiols / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism*
chemical_list: D026403:S-Nitrosothiols; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D009599:Nitroprusside; D009569:Nitric Oxide; D002118:Calcium
keywords: Apoptosis; Ca(2+); Nitric oxide; Osteoblast; S-nitrosylation; TRPV1