INTERACTION OF CAVEOLIN-1, NITRIC OXIDE, AND NITRIC OXIDE SYNTHASES IN HYPOXIC HUMAN SK-N-MC NEUROBLASTOMA CELLS.
J Neurochem. 2008 Aug 20;
Authors: Shen J, Lee W, Li Y, Lau CF, Ng KM, Fung ML, Liu KJ
Neuroblastoma cells are capable of hypoxic adaptation, but the mechanisms involved are not fully understood. We hypothesized that caveolin-1, a plasma membrane signal molecule, might play a role in protecting neuroblastoma cells from oxidative injury by modulating nitric oxide (NO) production. We investigated the alterations of caveolin-1, caveolin-2, nitric oxidase synthases (NOS) and NO levels in human SK-N-MC neuroblastoma cells exposed to hypoxia with 2% [O(2)]. The major discoveries include: (1) Caveolin-1 but not caveolin-2 was up-regulated in the cells exposed to 15 hours of hypoxia; (2) NO donor DETA/NO up-regulated the expression of caveolin-1, whereas the non-selective NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) and inducible NOS inhibitor 1400W each abolished the increase of caveolin-1 expression in the hypoxic SK-N-MC cells. These results suggest that iNOS-induced NO production contributes to the upregulation of caveolin-1 in the hypoxic SK-N-MC cells. Furthermore, we studied the roles played by caveolin-1 in regulating NO, NOS, and apoptotic cell death in the SK-N-MC cells subjected to 15 hrs of hypoxic treatment. Both caveolin-1 transfection and caveolin-1 scaffolding domain (CSD peptide) abolished the induction of iNOS, reduced the production of NO, and reduced the rates of apoptotic cell death in the hypoxic SK-N-MC cells. These results suggest that increased expression of caveolin-1 in response to hypoxic stimulation could prevent oxidative injury induced by reactive oxygen species. The interactions of caveolin-1, NO, and NOS could be an important signal pathway in protecting the neuroblastoma cells from oxidative injury, contributing to the hypoxic tolerance of neuroblastoma cells.
PMID: 18717816 [PubMed - as supplied by publisher]
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