Nitric oxide stimulates myoglobin gene and protein expression in vascular smooth muscle

Benjamin S. Rayner, Susan Hua, Tharani Sabaretnam, Paul K. Witting*

*Corresponding author for this work

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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 bNO (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 μM) of •NO from the donors diethylamineNONOate or spermine-NONOate (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°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.

Original languageEnglish
Pages (from-to)169-177
Number of pages9
JournalBiochemical Journal
Volume423
Issue number2
DOIs
Publication statusPublished - 15 Oct 2009
Externally publishedYes

Keywords

  • Endothelial function
  • Haem protein
  • Nitric oxide metabolism
  • Vascular smooth muscle
  • Vasodilation

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