2 GENES CONTRIBUTE TO DIFFERENT EXTENTS TO THE HEME OXYGENASE ENZYME-ACTIVITY MEASURED IN CULTURED HUMAN SKIN FIBROBLASTS AND KERATINOCYTES- IMPLICATIONS FOR PROTECTION AGAINST OXIDANT STRESS

Activation of expression of the heme oxygenase (HO) gene appears to be involved in a cellular defense system in mammalian cells. We now demo nstrate that while HO-1 mRNA levels are strongly inducible in dermal f ibroblasts they are barely inducible in human epidermal keratinocytes following oxidative stress (UVA radiation and hydrogen peroxide). Para lleling this result was the observation that HO-2 mRNA levels were low in dermal fibroblasts but were high in epidermal keratinocytes. In ne ither case was the HO-2 gene inducible. The expression of the two HO g enes led to enzymatic activity in both types of skin cells with an app roximately 2.5-fold higher level of enzymatic activity present in kera tinocytes compared with fibroblasts derived from the same biopsy. In a ddition, ferritin levels, which have been found to be augmented via th e HO-dependent release of iron from endogenous heme sources, were two- to three-fold higher in keratinocytes compared with matching fibrobla sts. This higher ferritin pool would result in an enhancement of cellu lar iron sequestering capacity that may confer increased resistance to oxidative stress. Indeed, keratinocytes showed less UVA radiation-dep endent cell membrane damage than fibroblasts. These results are consis tent with the hypothesis that HO expression in human epidermis and der mis is related to cellular defense mechanisms that operate in human sk in.