Cytoglobin is expressed in the vasculature and regulates cell respiration and proliferation via nitric oxide dioxygenation.
Disposition of the second messenger nitric oxide (NO) in mammalian tissues occurs through multiple pathways including dioxygenation by erythrocyte hemoglobin and red muscle myoglobin. Metabolism by a putative NO dioxygenase activity in non-striated tissues has also been postulated, but the exact nature of this activity is unknown. In the present study, we tested the hypothesis that cytoglobin, a newly discovered hexacoordinated globin, participates in cell-mediated NO consumption. Stable expression of small hairpin RNA targeting cytoglobin in fibroblasts resulted in decreased NO consumption and intracellular nitrate production. These cells were more sensitive to NO-induced inhibition of cell respiration and proliferation, which could be restored by re-expression of human cytoglobin. We also demonstrated cytoglobin expression in adventitial fibroblasts as well as vascular smooth muscle cells from various species including human and found that cytoglobin was expressed in the adventitia and media of intact rat aorta. These results indicate that cytoglobin contributes to cell-mediated NO dioxygenation and represents an important NO sink in the vascular wall.
Halligan
Katharine E
KE
Center for Cardiovascular Sciences, Albany Medical College, Albany, New York 12208.
Jourd'heuil
Frances L
FL
Jourd'heuil
David
D
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism*; D049109:Cell Proliferation; D003238:Connective Tissue / Q000378:metabolism; D000078842:Cytoglobin; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D005914:Globins / Q000096:biosynthesis*; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D041681:NIH 3T3 Cells; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology*; D051381:Rats
C000627265:CYGB protein, human; C000627267:Cygb protein, mouse; C000627268:Cygb protein, rat; D000078842:Cytoglobin; D009566:Nitrates; D009569:Nitric Oxide; D005914:Globins