GSBS Student Publications

Title

Repression of ALA synthase by heme and zinc-mesoporphyrin in a chick embryo liver cell culture model of acute porphyria

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Medicine

Date

6-1-1994

Document Type

Article

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

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

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.

Related Resources

Link to Article in PubMed

Journal Title

European journal of clinical investigation

PubMed ID

7957494