Light induced heme oxygenase 1 is suppressed by Bach1 in human skin keratinocytes

Ultraviolet A (UVA) radiation is an oxidizing agent that strongly induces the heme oxygenase 1(HO-1) expression in cultured human skin fibroblasts, but weakly induces it in skin keratinocytes. Low basal levels of HO-1 and much higher basal levels of HO-2 protein were observed in keratinocytes compared with fibroblasts. Here we found that increase of HO-2 reduces basal and UVA-induced HO-1 levels. Silencing of Bach1 strongly increased HO-1 levels in HaCaT transformed keratinocytes and these HO-1 levels were not further increased by UVA irradiation. This is consistent with the conclusion that high constitutive levels of HO-2 expression in keratinocytes are responsible for the resistance of these cells to HO-1 induction by UVA radiation and that Bach1 plays a predominant role in influencing the lack of HO-1 expression in keratinocytes. Bach1 inhibition reduced the 500 kJ/m(2) UVA-induced cell death measured by MTS viability assays. These results suggest that Bach1 inhibition protect against high dose of UVA irradiation induced cell damage in skin keratinocytes.