Age-dependent increase of heme oxygenase-1 gene expression in the liver mediated by NF kappa B

Heme, the iron-porphyrin coordination complex, released from the degradatio n of hemoproteins, is a strong prooxidant. It is enzymatically degraded by heme oxygenase to free iron, carbon monoxide and biliverdin. Biliverdin and its reduced metabolite bilirubin are two potent physiological antioxidants . Here we show a progressive increase of steady-state levels of the mRNA en coding the inducible isoform of this enzyme (heme oxygenase-1) in the rat l iver during aging. We had previously reported that aging is associated with increased activation of the nuclear factor kappa B (NF kappa B). We now pr ovide evidence to establish that overexpression of NF kappa B in transfecte d liver-derived HepG2 cells can cause a marked induction of the endogenous heme oxygenase-1 (HO-1) mRNA and activation of the cotransfected HO-1 gene promoter. Taken together, these results support the conclusion that enhance d oxidative stress during aging is accompanied by compensatory induction of the antioxidant enzyme HO-1 through activation of the NF kappa B pathway. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.