title: Nitric oxide down-regulates caveolin-1 expression in rat brains during focal cerebral ischemia and reperfusion injury.
abstract: As a signalling molecule of the integral membrane protein family, caveolin participates in cellular signal transduction via interaction with other signalling molecules. The nature of interaction between nitric oxide (NO) and caveolin in the brain, however, remains largely unknown. In this study we investigated the role(s) of NO in regulating caveolin-1 expression in rat ischemic brains with middle cerebral artery occlusion (MCAO). Exposure to 1 h ischemia induced the increases in neuronal nitric oxide synthase (nNOS) and NO concentration with concurrent down-regulation of caveolin-1 expression in the ischemic core of rat brains. Subsequent 24 h or more reperfusion time led to an increase in inducible NOS (iNOS) expression and NO production, as well as a decline of caveolin-1 protein at the core and penumbra of the ischemic brain. Afterwards, NOS inhibitors and an NO donor were utilized to clarify the link between NO production and caveolin-1 expression in the rats with 1 h ischemia plus 24 h reperfusion. N(G)-nitro-l-arginine methyl ester (L-NAME, a non-selective NOS inhibitor), N(6)-(1-iminoethyl)-lysine (NIL, an iNOS inhibitor), and 7-nitroindazole (7-NI, a nNOS inhibitor) prevented the loss of caveolin-1 in the core and penumbra of the ischemic brain, whereas l-N(5)-(1-iminoethyl)-ornithine (L-NIO, an endothelial NOS inhibitor) showed less effect than the other NOS inhibitors. S-Nitroso-N-acetylpenicillamine (SNAP, a NO donor) down-regulated the expression of caveolin-1 protein in normal and ischemic brains. These results, when taken together, suggest that NO modulates the expression of caveolin-1 in the brain and that the loss of caveolin-1 is associated with NO production in the ischemic brain.
authors.affiliation: School of Chinese Medicine, Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
authors.forename: Jiangang
authors.initials: J
authors.lastname: Shen
authors.forename: Stephanie
authors.initials: S
authors.lastname: Ma
authors.forename: Puishan
authors.initials: P
authors.lastname: Chan
authors.forename: Waisin
authors.initials: W
authors.lastname: Lee
authors.forename: Peter C W
authors.initials: PC
authors.lastname: Fung
authors.forename: Raymond T F
authors.initials: RT
authors.lastname: Cheung
authors.forename: Yao
authors.initials: Y
authors.lastname: Tong
authors.forename: Ke Jian
authors.initials: KJ
authors.lastname: Liu
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology*; D051242:Caveolin 1 / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009952:Ornithine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology*
chemical_list: D051242:Caveolin 1; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; C065027:N(G)-iminoethylornithine; D009952:Ornithine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester