Oxidant-mediated impairment of nitric oxide signaling in sickle cell disease - Mechanisms and consequences
CELLULAR AND MOLECULAR BIOLOGY, vol.50, no.1, pp.95-105, 2004 (SCI-Expanded, Scopus)
- Publication Type: Article / Review
- Volume: 50 Issue: 1
- Publication Date: 2004
- Journal Name: CELLULAR AND MOLECULAR BIOLOGY
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Page Numbers: pp.95-105
- Keywords: sickle cell disease, nitric oxide, xanthine oxidase, reactive species, nitration, MAMMARY EPITHELIAL-CELLS, TRANSGENIC MOUSE MODEL, ACTIN-BINDING PROTEINS, TUMOR-NECROSIS-FACTOR, ACUTE CHEST SYNDROME, XANTHINE-OXIDASE, REPERFUSION INJURY, ENDOTHELIAL-CELLS, GENE-EXPRESSION, VASCULAR OCCLUSION
- Akdeniz University Affiliated: Yes
Abstract
In addition to its mediation of vascular relaxation and neurotransmission, nitric oxide ((NO)-N-.) potently modulates oxygen radical reactions and inflammatory signaling. This participation of (NO)-N-. in free radical and oxidative reactions will yield secondary oxides of nitrogen that display frequently-undefined reactivities and unique signaling properties. In sickle cell disease (SCD) inflammatory-derived oxidative reactions impair (NO)-N-.-dependent vascular function. A combination of clinical and knockout-transgenic SCD mouse studies show increased rates of xanthine oxidase-dependent superoxide (O-2(.-)) production and reveal the presence of an oxidative and nitrative inflammatory milieu in the sickle cell vasculature, kidney and liver. Considering the critical role of endothelial (NO)-N-. production in regulating endothelial adhesion molecule expression, platelet aggregation, and both basal and stress-mediated vasodilation, the O-2(.-) mediated reduction in (NO)-N-. bioavailability can significantly contribute to the vascular dysfunction and organ injury associated with SCD.