Differential effects of metalloporphyrins on messenger RNA levels of delta-aminolevulinate synthase and heme oxygenase. Studies in cultured chick embryo liver cells
Authors
Cable, Edward EarlPepe, Joyce A.
Karamitsios, Nicholas C.
Lambrecht, Richard W.
Bonkovsky, Herbert L.
UMass Chan Affiliations
Graduate School of Biomedical SciencesDocument Type
Journal ArticlePublication Date
1994-08-01Keywords
5-Aminolevulinate Synthetase; Animals; Cells, Cultured; Chick Embryo; Heme Oxygenase (Decyclizing); Liver; Metalloporphyrins; RNA, MessengerLife Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
The acute porphyrias in relapse are commonly treated with intravenous heme infusion to decrease the activity of delta-aminolevulinic acid synthase, normally the rate-controlling enzyme in heme biosynthesis. The biochemical effects of heme treatment are short-lived, probably due in part to heme-mediated induction of heme oxygenase, the rate-controlling enzyme for heme degradation. In this work, selected nonheme metalloporphyrins were screened for their ability to reduce delta-aminolevulinic acid synthase mRNA and induce heme oxygenase mRNA in chick embryo liver cell cultures. Of the metalloporphyrins tested, only zinc-mesoporphyrin reduced delta-aminolevulinic acid synthase mRNA without increasing heme oxygenase mRNA. The combination of zinc-mesoporphyrin and heme, at nanomolar concentrations, decreased delta-aminolevulinic acid synthase mRNA in a dose-dependent manner. The combination of zinc-mesoporphyrin (50 nM) and heme (200 nM) decreased the half-life of the mRNA for delta-aminolevulinic acid synthase from 5.2 to 2.5 h, while a similar decrease was produced by heme (10 microM) alone (2.2 h). The ability of zinc-mesoporphyrin to supplement the reduction of delta-aminolevulinic acid synthase mRNA by heme, in a process similar to that observed with heme alone, provides a rationale for further investigation of this compound for eventual use as a supplement to heme therapy of the acute porphyrias and perhaps other conditions in which heme may be of benefit.Source
J Clin Invest. 1994 Aug;94(2):649-54. Link to article on publisher's siteDOI
10.1172/JCI117381Permanent Link to this Item
http://hdl.handle.net/20.500.14038/33095PubMed ID
8040318Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1172/JCI117381