EurekaMag.com logo
+ Translate

Regulation of hepatic heme metabolism disparate mechanisms of induction of heme oxygenase by drugs and metals


, : Regulation of hepatic heme metabolism disparate mechanisms of induction of heme oxygenase by drugs and metals. Biochemical Journal 250(1): 189-196

We studied drug- and metal-mediated increases in activity of haem oxygenase, the rate-controlling enzyme for haem breakdown, in chick-embryo hepatocytes in ovo and in primary culture. Phenobarbitone and phenobarbitone-like drugs (glutethimide, mephenytoin), which are known to increase concentrations of an isoform of cytochrome P-450 in chick-embryo hepatocytes, were found to increase activities of haem oxygenase as well. In contrast, 20-methylcholanthrene, which increases the concentration of a different isoform of cytochrome P-450, had no effect on activity of haem oxygenase. Inhibitors of haem synthesis, 4,6-dioxoheptanoic acid or desferrioxamine, prevented drug-mediated induction of both cytochrome P-450 and haem oxygenase in embryo hepatocytes in ovo or in culture. Addition of haem restored induction of both enzymes. These results are interpreted to indicate that phenobarbitone and its congeners induce haem oxygenase by increasing hepatic haem formation. In contrast, increases in haem oxygenase activity by metals such as cobalt, cadmium and iron were not dependent on increased haem synthesis and were not inhibited by 4,6-dioxoheptanoic acid. We conclude that (1) induction of hepatic haem oxygenase activity by phenobarbitone-type drugs is due to increased haem formation, and (2) induction of haem oxygenase by drugs and metals occurs by different mechanisms.

(PDF 0-2 workdays service)

Accession: 006288410

PMID: 3355510

Submit PDF Full Text: Here


Submit PDF Full Text

No spam - Every submission is manually reviewed

Due to poor quality, we do not accept files from Researchgate

Submitted PDF Full Texts will always be free for everyone
(We only charge for PDFs that we need to acquire)

Select a PDF file:
Close
Close

Related references

Lincoln, B.C.; Healey, J.F.; Bonkovsky, H.L., 1988: Regulation of hepatic haem metabolism. Disparate mechanisms of induction of haem oxygenase by drugs and metals. We studied drug- and metal-mediated increases in activity of haem oxygenase, the rate-controlling enzyme for haem breakdown, in chick-embryo hepatocytes in ovo and in primary culture. Phenobarbitone and phenobarbitone-like drugs (glutethimide, mep...

Maines, M.D.; Kappas, A., 1976: The induction of heme oxidation in various tissues by trace metals: evidence for the catabolism of endogenous heme by hepatic heme oxygenase. Cobalt is a potent inducer of hepatic heme oxygenase and concomitantly decreases microsomal cytochrome P-450 content in liver cells. Studies in which microsomal heme was labelled with 14C-beta-aminolevulinic acid showed that the decline observed i...

Lincoln B.C.; Healey J.F.; Bonkovsky H.L., 1987: Regulation of hepatic heme metabolism heme oxygenase is induced by at least two different mechanisms. Hepatology 7(5): 1053

Maines, M.D.; Kappas, A., 1976: Selenium regulation of hepatic heme metabolism: induction of delta-aminolevulinate synthase and heme oxygenase. Selenium was found to be a novel regulator of cellular heme methabolism in that the element induced both the mitochondrial enzyme delta-aminolevulinate synthase [succinyl-CoA:glycine C-succinyltransferase (decarboxylating); EC 2-3-1-37] and the mi...

Maines, M.D.; Kappas, A., 1976: Selenium regulation of hepatic heme metabolism induction of delta amino levulinate synthase ec 2.3.1.37 and heme oxygenase ec 1.14.99.3. Se was a novel of regulator of cellular [rat] heme metabolism in that the element induced both the mitochondrial enzyme .delta.-aminolevulinate synthase [succinyl-CoA:glycine C-succinyltransferase (decarboxylating); EC 2.3.1.37] and the microsomal...

Cable, E.E.; Miller, T.G.; Isom, H.C., 2001: Regulation of heme metabolism in rat hepatocytes and hepatocyte cell lines: delta-aminolevulinic acid synthase and heme oxygenase are regulated by different heme-dependent mechanisms. Regulation of delta-aminolevulinic acid (ALA) synthase and heme oxygenase was analyzed in primary rat hepatocytes and in two immortalized cell lines, CWSV16 and CWSV17 cells. ALA synthase was induced by 4,6-dioxohepatnoic acid (4,6-DHA), a specifi...

Kutty R.K.; Maines M.D., 1984: Hepatic heme metabolism possible role of biliverdin in the regulation of heme oxygenase activity. Treatment of rats with biliverdin (48 h) resulted in an increase in microsomal heme oxygenase activity in the liver. This was accompanied by decreases in the microsomal heme and cytochrome P-450 contents. In these respects, the cellular responses...

Cable, E.E.; Kuhn, B.R.; Isom, H.C., 2001: Regulation of human hepatic DELTA-aminolevulinate synthase and heme oxygenase by heme and non-heme metalloporphyrins. Hepatology 34(4 Pt 2): 356A, October

Paterniti J.R.Jr; Lin C I.P.; Beattie D.S., 1980: Regulation of heme metabolism during senescence activity of several heme containing enzymes and heme oxygenase in the liver and kidney of aging rats. The activities of several heme-containing enzymes plus succinate dehydrogenase, the content of mitochondrial cytochromes, the amount of microsomal cytochrome P-450, and the activity of heme oxygenase, the major enzyme of heme degradation, have bee...

Alam, J.; Cai, J.; Smith, A., 1994: Isolation and characterization of the mouse heme oxygenase-1 gene. Distal 5' sequences are required for induction by heme or heavy metals. Mouse genomic fragments encoding heme oxygenase-1 (HO-1) were isolated from a recombinant lambda library by in situ plaque hybridization. The mouse HO-1 gene, approximately 7 kilobase pairs (kbp) in length, is organized into 5 exons and 4 introns....