Nitric Oxide Preconditioning Regulates Endothelial Monolayer Integrity Via the Heat Shock Protein 90-soluble Guanylate Cyclase Pathway.
From: Vascular Biology Center, Medical College of Georgia, Augusta, GA, 30912-2500, USA. gantonova@mail.mcg.edu
American journal of physiology. Heart and circulatory physiology
- Publish Date: Feb 2007
- ISSN: 0363-6135
- Volume: 292
- Issue: 2
- Pages: H893-903
- Medium: Print
- Language: English
- Citation (JAMA): Antonova Galina N, Snead Connie M, Antonov Alexander S, et al. Nitric Oxide Preconditioning Regulates Endothelial Monolayer Integrity Via the Heat Shock Protein 90-soluble Guanylate Cyclase Pathway.. Am. J. Physiol. Heart Circ. Physiol. Feb 2007;292:H893-903
Abstract
Large (pathological) amounts of nitric oxide (NO) induce cell injury, whereas low (physiological) NO concentrations often ameliorate cell injury. We tested the hypotheses that pretreatment of endothelial cells with low concentrations of NO (preconditioning) would prevent injury induced by high NO concentrations. Apoptosis, induced in bovine aortic endothelial cells (BAECs) by exposing them to either 4 mM sodium nitroprusside (SNP) or 0.5 mM N-(2-aminoethyl)-N-(2-hydroxy-2-nitrosohydrazino)-1,2-ethylenediamine (spermine NONOate) for 8 h, was abolished by 24-h pretreatment with either 100 microM SNP, 10 microM spermine NONOate, or 100 microM 8-bromo-cGMP (8-Br-cGMP). Repair of BAECs following wounding, measured as the recovery rate of transendothelial electrical resistance, was delayed by 8-h exposure to 4 mM SNP, and this delay was significantly attenuated by 24-h pretreatment with 100 microM SNP. NO preconditioning produced increased association and expression of soluble guanyl cyclase (sGC) and heat shock protein 90 (HSP90). The protective effect of NO preconditioning, but not the injurious effect of 4 mM SNP, was abolished by either a sGC activity inhibitor 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) or a HSP90 binding inhibitor (radicicol) and was mimicked by 8-Br-cGMP. We conclude that preconditioning with a low dose of NO donor accelerates repair and maintains endothelial integrity via a mechanism that includes the HSP90/sGC pathway. HSP90/sGC may thus play a role in the protective effects of NO-generating drugs from injurious stimuli.
Mesh Headings (Keywords): Animals, Aorta, Apoptosis, Cattle, Cells, Cultured, Cyclic GMP, Cyclic GMP-Dependent Protein Kinases, Dose-Response Relationship, Drug, Electric Impedance, Endothelial Cells, Enzyme Inhibitors, Guanylate Cyclase, HSP90 Heat-Shock Proteins, Microfilaments, Nitric Oxide, Nitric Oxide Donors, Nitroprusside, Oxadiazoles, Quinoxalines, Receptors, Cytoplasmic and Nuclear, Spermine, Time Factors, Wound Healing
Check for Full Text / PubMed Unique Identifier (PMID): 17012359
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