Mechanism of synergistic induction of hepatic heme oxygenase by glutethimide and iron: studies in cultured chick embryo liver cells.
Heme oxygenase, the rate controlling enzyme for heme catabolism, is inducible by a variety of treatments, some of which induce by a heme-dependent mechanism and others by a heme-independent mechanism. This work shows that, in cultured chick embryo liver cells, synergistic induction of heme oxygenase by iron, added with the phenobarbital-like drug, glutethimide was heme-dependent. Addition of an inhibitor of heme biosynthesis abolished the synergistic induction of heme oxygenase providing evidence for the heme-dependent mechanism of induction. Glutethimide and iron appeared to induce at the transcriptional level since both heme oxygenase mRNA and protein levels correlate with changes in heme oxygenase activity.
Cable
E
E
Department of Biochemistry, Emory University, Atlanta, GA 30322.
Greene
Y
Y
Healey
J
J
Evans
C O
CO
Bonkovsky
H
H
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002642:Chick Embryo; D004357:Drug Synergism; D004790:Enzyme Induction / Q000187:drug effects; D005290:Ferric Compounds / Q000494:pharmacology; D005984:Glutethimide / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis* / Q000235:genetics; D006537:Heptanoates / Q000494:pharmacology; D007501:Iron / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000096:biosynthesis*; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics
D005290:Ferric Compounds; D006537:Heptanoates; D012333:RNA, Messenger; C020804:succinylacetone; D005984:Glutethimide; D007501:Iron; D006899:Mixed Function Oxygenases; D006419:Heme Oxygenase (Decyclizing); D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate