Repression of ALA synthase by heme and zinc-mesoporphyrin in a chick embryo liver cell culture model of acute porphyria
Graduate School of Biomedical Sciences; Department of Medicine
Medical Subject Headings
5-Aminolevulinate Synthetase; Animals; Cells, Cultured; Chick Embryo; Dose-Response Relationship, Drug; Enzyme Repression; Ferric Compounds; Glutethimide; Heme; Heme Oxygenase (Decyclizing); Heptanoates; Kinetics; Liver; Metalloporphyrins; Nitrilotriacetic Acid; Porphyrias
Life Sciences | Medicine and Health Sciences
We characterize a liver cell culture model for acute hepatic porphyrias that recapitulates the biochemical features of the human syndrome. In chick embryo liver cells in primary culture exposed to glutethimide and 4,6-dioxoheptanoic acid, heme alone produced a transient dose-dependent decrease in delta-aminolevulinate synthase and a concomitant increase in heme oxygenase. The addition of low concentrations of zinc-mesoporphyrin (50-200 nM), an inhibitor of heme oxygenase, led to more prolonged decreases in activity of the synthase and to an additive effect with heme. These effects of zinc-mesoporphyrin were associated with prolonged inhibition of heme oxygenase. These results suggest that the treatment of choice of acute porphyric syndromes may be the combination of low doses of heme and zinc-mesoporphyrin or another similarly non-toxic inhibitor of heme oxygenase.
Rights and Permissions
Citation: Eur J Clin Invest. 1994 Jun;24(6):406-15.
European journal of clinical investigation
Russo, Shirley M.; Pepe, Joyce A.; Cable, Edward Earl; Lambrecht, Richard W.; and Bonkovsky, Herbert L., "Repression of ALA synthase by heme and zinc-mesoporphyrin in a chick embryo liver cell culture model of acute porphyria" (1994). GSBS Student Publications. 1057.