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.