Nitric oxide stimulates myoglobin gene and protein expression in vascular smooth muscle.
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 (nitric oxide) homoeostasis through (i) binding *NO (Mb-NO complex); (ii) oxidation of *NO to nitrate; and (iii) formation of vasoactive S-nitroso-Mb [Rayner, B.S., Wu, B.-J., Raftery, M., Stocker, R. and Witting, P.K. (2005) J. Biol. Chem. 280, 9985-9993]. Pathological *NO 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 microM) of *NO 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 doses tested. Importantly, sub-culturing isolated rat aortic segments for 7 days in the presence of L-arginine at 37 degrees C stimulated *NO 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 promotes an up-regulation of the Mb gene and protein, suggesting a feedback relationship between *NO 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.
Rayner
Benjamin S
BS
Vascular Biology Group, ANZAC Research Institute, Concord Hospital, Concord, NSW, Australia.
Hua
Susan
S
Sabaretnam
Tharani
T
Witting
Paul K
PK
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018929:Cell Culture Techniques; D002462:Cell Membrane / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009211:Myoglobin / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology*; D051381:Rats; D015854:Up-Regulation / Q000187:drug effects
D009211:Myoglobin; D009569:Nitric Oxide