Involvement of the heme oxygenase-carbon monoxide pathway in keratinocyte proliferation.
It has been suggested that nitric oxide (NO), a small gaseous molecule with a multiplicity of cellular functions, plays an important part in the regulation of cellular proliferation. We have examined the effect of the NO donor sodium nitroprusside (SNP) on heme oxygenase-1 (HO-1) expression in human epidermal keratinocytes and investigated the contribution of the heme oxygenase pathway in the control of keratinocyte proliferation. Incubation of keratinocytes with 0.5 mM SNP resulted in a 2.5-fold increase in heme oxygenase activity which was reflected by a significant increase in HO-1 protein expression, as measured by Western blot. This effect was associated with a 200% increase in keratinocyte proliferation. The proliferative effect of the NO donor was totally abolished by co-incubation of SNP with tin protoporphyrin IX, a potent inhibitor of heme oxygenase, or hydroxocobalamin, a NO scavenger. These results suggest that the heme oxygenase pathway is involved in keratinocyte proliferation mediated by NO.
Clark
J E
JE
Department of Surgical Research, Northwick Park Institute for Medical Research, Harrow, Middlesex, United Kingdom. j.e.clark@ic.ac.uk
Green
C J
CJ
Motterlini
R
R
D002248:Carbon Monoxide / Q000378:metabolism*; D002455:Cell Division; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006427:Hemin / Q000494:pharmacology; D006801:Humans; D006879:Hydroxocobalamin / Q000494:pharmacology; D015603:Keratinocytes / Q000502:physiology*; D008565:Membrane Proteins; D008665:Metalloporphyrins / Q000494:pharmacology; D008954:Models, Biological; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D011524:Protoporphyrins / Q000494:pharmacology
D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D008665:Metalloporphyrins; D011524:Protoporphyrins; D009599:Nitroprusside; D009569:Nitric Oxide; D006427:Hemin; D002248:Carbon Monoxide; C032628:tin protoporphyrin IX; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D006879:Hydroxocobalamin