Up-regulation of heme oxygenase 1 (HO-1) by ultraviolet A (UVA; 320-380 nm) 
irradiation of human skin cells protects them against oxidative stress. The role 
of Nrf2 in up-regulation of HO-1 and other phase II genes is well established. 
The mechanism underlying Bach1-mediated HO-1 repression is less well understood 
although cellular localization seems to be crucial. Because prolonged HO-1 
overexpression is likely to be detrimental, it is crucial that activation of the 
gene is transient. We now show that UVA irradiation of cultured human skin 
fibroblasts enhances accumulation of Bach1 mRNA and protein severalfold. 
Endogenous Bach1 protein accumulates in the nucleus after 8h and may occupy MARE 
sites after HO-1 activation thus providing a compensatory mechanism to control 
HO-1 overexpression. Overexpression of Bach1, together with MafK, represses 
basal and UVA-mediated HO-1 protein expression, whereas silencing of the Bach1 
gene by Bach1-specific siRNAs causes robust enhancement of constitutive HO-1 
levels. UVA treatment of cells in which Bach1 has been silenced leads to higher 
levels of induction of the HO-1 protein. Although Bach1 protein is exported from 
the nucleus 12h after UVA irradiation, the release of free cellular heme from 
microsomal heme-containing proteins is immediate rather than delayed. Although 
heme does promote the export of Bach1 via the Crm1/exportin 1 pathway and is 
involved in the delayed UVA-mediated export of the protein, it is not clear how 
this occurs.