Journal
BIOCHEMICAL JOURNAL
Volume 423, Issue -, Pages 169-177Publisher
PORTLAND PRESS LTD
DOI: 10.1042/BJ20090716
Keywords
endothelial function; haem protein; nitric oxide metabolism; vascular smooth muscle; vasodilation
Categories
Funding
- ARC (Australian Research Council)
- National Heart Foundation of Australia
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Mb (myoglobin) is a haemoprotein present in cardiac, skeletal and smooth muscle and is primarily responsible for the storage and 'facilitated transfer' of molecular oxygen from the cell membrane to mitochondria. Also, Mb plays a role in regulating (NO)-N-center dot (nitric oxide) homoeostasis through (i) binding (NO)-N-center dot (Mb-NO complex); (ii) oxidation of (NO)-N-center dot to nitrate; and (iii) formation of vasoactive S-nitroso-Mb [Rayner, B.S., Wu, B.-J., Raftery, M., Stocker, R. and Witting, RK. (2005) J. Biol. Chem. 280, 9985-9993]. Pathological (NO)-N-center dot concentrations affect mitochondrial function and decrease cell viability through inducing apoptosis. Treatment of cultured rat VSMCs (vascular smooth muscle cells) with cumulative doses (0.1, 1 or 10 mu M) of (NO)-N-center dot from the donors diethylamineNONOate or spermineNONOate (N-[2-aminoethyl]-N-[2-hydroxy-3-nitrosohydrazine]-1,2-ethelenediamine) yielded a time-dependent increase in Mb gene expression. Concomitant transcriptional activation increased the concentration of Mb within cultured rat or primary human VSMCs as judged by Western blot analysis and indirect immunofluorescence microscopy. Cell viability did not decrease in these cells at the (NO)-N-center dot doses tested. Importantly, sub-culturing isolated rat aortic segments for 7 days in the presence of L-arginine at 37 degrees C stimulated (NO)-N-center dot production with a parallel increase in Mb in the underlying VSMCs. Overall, exposure of VSMCs (either in cell culture or intact vessels) to pathological (NO)-N-center dot promotes an up-regulation of the Mb gene and protein, suggesting a feedback relationship between (NO)-N-center dot and Mb that regulates the concentration of the potent cell signalling molecule in the vessel wall, similar to the role haemoglobin plays in the vessel lumen.
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