Age-dependent increase of heme oxygenase-1 gene expression in the liver mediated by NFkappaB.
Heme, the iron-porphyrin coordination complex, released from the degradation 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 encoding the inducible isoform of this enzyme (heme oxygenase-1) in the rat liver during aging. We had previously reported that aging is associated with increased activation of the nuclear factor kappaB (NFkappaB). We now provide evidence to establish that overexpression of NFkappaB in transfected 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 enhanced oxidative stress during aging is accompanied by compensatory induction of the antioxidant enzyme HO-1 through activation of the NFkappaB pathway.
Lavrovsky
Y
Y
Department of Cellular and Structural Biology, The University of Texas Health Science Center, 7703 Floyd Curl Drive at San Antonio, San Antonio, TX 78284, USA. lavrosky@uthscsa.edu
Song
C S
CS
Chatterjee
B
B
Roy
A K
AK
D000818:Animals; D015971:Gene Expression Regulation, Enzymologic; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D051547:Heme Oxygenase-1; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D008565:Membrane Proteins; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051381:Rats; D011916:Rats, Inbred F344; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D008565:Membrane Proteins; D016328:NF-kappa B; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2