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Titolo:
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
Autore:
Cable, EE; Miller, TG; Isom, HC;
Indirizzi:
Penn State Univ, Coll Med, Dept Microbiol & Immunol, Hershey, PA 17033 USAPenn State Univ Hershey PA USA 17033 iol & Immunol, Hershey, PA 17033 USA Penn State Univ, Coll Med, Dept Pathol, Hershey, PA 17033 USA Penn State Univ Hershey PA USA 17033 , Dept Pathol, Hershey, PA 17033 USA
Titolo Testata:
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
fascicolo: 2, volume: 384, anno: 2000,
pagine: 280 - 295
SICI:
0003-9861(200012)384:2<280:ROHMIR>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
EMBRYO LIVER-CELLS; CHEMICALLY DEFINED MEDIUM; MESSENGER-RNA; 5-AMINOLEVULINATE SYNTHASE; PRIMARY CULTURES; PHENOBARBITAL INDUCTION; SYNERGISTIC INDUCTION; GENE-EXPRESSION; SIMIAN VIRUS-40; ACUTE PORPHYRIA;
Keywords:
ALA synthase; heme; heme oxygenase; mRNA stability; porphyria; rat hepatocytes;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
75
Recensione:
Indirizzi per estratti:
Indirizzo: Isom, HC Penn State Univ, Coll Med, Dept Microbiol & Immunol, 500 Univ Dr,Hershey,PA 17033 USA Penn State Univ 500 Univ Dr Hershey PA USA 17033 hey,PA 17033 USA
Citazione:
E.E. Cable et al., "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", ARCH BIOCH, 384(2), 2000, pp. 280-295

Abstract

Regulation of delta -aminolevulinic acid (ALA) synthase and heme oxygenasewas 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 specific inhibitor of ALA dehydratase, in all three systems; however, the induction in CWSV17 cells was greater than in either of theother two systems. Therefore, CWSV17 cells were used to explore the regulation of both enzymes by heme and 4,6-DHA Data obtained from detailed concentration curves demonstrated that 4,6-DHA induced the activity of ALA synthase once ALA dehydratase activity became rate-limiting for heme biosynthesis. Heme induced heme oxygenase activity with increases occurring at concentrations of 10 muM or greater. Heme blocked the 4,6-DHA-dependent induction of ALA synthase with an EC50 of 1.25 muM. Heme dependent decreases of AW synthase mRNA levels occurred more quickly and at lower concentrations than heme-dependent increases of heme oxygenase mRNA levels, ALA synthase mRNA remained at reduced levels for extended periods of time, while the increases in heme oxygenase mRNA mere much more transient, The drastic differences in concentrations and times at which heme-dependent effects were observed strongly suggest that two-different heme-dependent mechanisms control the ALA synthase and heme oxygenase mRNAs. In CWSV17 cells, heme decreased the stability of;ALA synthase mRNA from 2.5 to 1.3 h, while 4,6-DHA increased the stability of the mRNA to 5.2 h, These studies demonstrate that regulation of ALA synthase mRNA levels by heme in a mammalian system is mediated by a change in ALA synthase mRNA stability. The results reported here demonstrate the function of the regulatory heme pool on both ALA synthase and heme oxygenase in a mammalian hepatocyte system, (C) 2000 Academic Press.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 10/07/20 alle ore 09:41:58