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975869 
Journal Article 
Abstract 
Cytoglobin regulates cell respiration and nitrosative stress through NO dioxygenation and co-localizes with inducible nitric oxide synthase during vascular injury 
Halligan, K; Jourd'heuil, F; Vincent, C; Jourd'heuil, D 
2008 
Yes 
Free Radical Biology and Medicine
ISSN: 0891-5849
EISSN: 1873-4596 
45 
Suppl. 
S144-S144 
English 
WOS:000260867900407 
is part of a larger document 3452652 SFRBM's 15th Annual Meeting: Program and Abstracts
Disposition of the second messenger nitric oxide (NO) in mammalian tissues occurs through multiple pathways including reaction with erythrocyte hemoglobin, red muscle myoglobin, and metabolism by NO dioxygenase activities in non-striated tissues. Although the newly discovered globin cytoglobin binds molecular oxygen and dioxygenates NO in vitro, the lack of an associated reductase activity has raised doubts about the ability of cytoglobin to dioxygenate NO in vivo. to elucidate the role of cytoglobin in NO metabolism, we stably expressed short hairpin RNA targeting cytoglobin in mouse fibroblasts. This resulted in a 80 percent reduction in cytoglobin protein expression. Wild type cells demonstrated intracellular nitrate generation upon addition of exogenous NO that was oxygen-dependent and cyanideinhibitable. the sustained dioxygenation of NO observed over a 30 min exposure to NO was diminished in cells with low cytoglobin expression. Protein nitrosation and heme-nitrosylation were increased in the absence of cytoglobin. These cells were also more sensitive to NO-induced inhibition of cell respiration. Normal response to NO could be re-established through expression of human cytoglobin in the knock down cells. We next determined that cytoglobin was expressed in primary aortic adventitial fibroblasts and smooth muscle cells from various species including humans. Cytoglobin content was also determined in rat carotid arteries after balloon-angioplasty injury in which extensive co-localization of cytoglobin with inducible nitric oxide synthase in neointimal vascular smooth muscle cells was observed. In summary, our study reveals a pivotal role for cytoglobin in cell-mediated NO dioxygenation to regulate nitrosative stress and cell respiration during conditions of chronic inflammation such as vascular injury. 
Society for Free Radical Biology and Medicine 15th Annual Meeting 
Indianapolis, IN 
November 19-23, 2008