دورية أكاديمية
Molecular basis for heme-dependent induction of heme oxygenase in primary cultures of chick embryo hepatocytes. Demonstration of acquired refractoriness to heme.
| العنوان: | Molecular basis for heme-dependent induction of heme oxygenase in primary cultures of chick embryo hepatocytes. Demonstration of acquired refractoriness to heme. |
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| المؤلفون: | Srivastava KK; Department of Medicine, University of Massachusetts Medical Center, Worcester 01655., Cable EE, Donohue SE, Bonkovsky HL |
| المصدر: | European journal of biochemistry [Eur J Biochem] 1993 May 01; Vol. 213 (3), pp. 909-17. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: Blackwell Science Ltd. on behalf of the Federation of European Biochemical Societies Country of Publication: England NLM ID: 0107600 Publication Model: Print Cited Medium: Print ISSN: 0014-2956 (Print) Linking ISSN: 00142956 NLM ISO Abbreviation: Eur J Biochem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: -2004: Oxford, UK : Blackwell Science Ltd. on behalf of the Federation of European Biochemical Societies Original Publication: Berlin, New York, Springer. |
| مواضيع طبية MeSH: | Heme/*pharmacology , Heme Oxygenase (Decyclizing)/*biosynthesis , Liver/*enzymology, Animals ; Cells, Cultured ; Chick Embryo ; Dose-Response Relationship, Drug ; Enzyme Induction/drug effects ; Heme Oxygenase (Decyclizing)/genetics ; RNA, Messenger/genetics ; RNA, Messenger/metabolism |
| مستخلص: | The effects of heme on the induction of mRNA and protein synthesis for heme oxygenase-1 have been studied in primary cultures of chick embryo liver cells. Heme increased the amount of mRNA and the rate of heme oxygenase-1-gene transcription in a dose-dependent fashion, with a maximal 20-fold increase occurring at 20 microM heme. The largest increase in the rate of transcription, measured by nuclear run-on assays, occurred at 5 h, 2 h earlier than the maximum increase in the amount of mRNA, measured by densitometry of Northern blots. 7-15 h after heme addition, the half-life of heme-oxygenase-1 mRNA was 3.5 h in the presence or absence of actinomycin D. In contrast, addition of cycloheximide markedly increased the stability of the message (half-life = 18 h), suggesting that a short-lived protein plays a key role in modulating heme oxygenase-1 mRNA levels. The half-life of heme-induced heme-oxygenase-1 protein, measured by [35S]methionine labelling and immunoprecipitation, was 15 h. This long half-life of the protein can largely account for the additional finding that, following addition of heme, the amount of enzyme protein in the cells increased for 10 h, after which it remained essentially constant for 15 h. A striking finding was that, after an initial burst of heme-stimulated gene transcription, the cells became refractory to further heme-mediated induction. This acquired resistance could not be attributed to the following: a longer duration of culture time; cellular toxicity caused by heme; a lack of heme in the medium or the cells; secretion of heme-binding proteins into the medium, preventing further heme uptake; the induction of cellular heme catabolism sufficient to deplete cellular heme. Instead, the results suggest a down-regulation of the intracellular machinery required for heme-dependent induction of heme oxygenase-1. |
| معلومات مُعتمدة: | DK 38825 United States DK NIDDK NIH HHS |
| المشرفين على المادة: | 0 (RNA, Messenger) 42VZT0U6YR (Heme) EC 1.14.14.18 (Heme Oxygenase (Decyclizing)) |
| تواريخ الأحداث: | Date Created: 19930501 Date Completed: 19930708 Latest Revision: 20190620 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1111/j.1432-1033.1993.tb17835.x |
| PMID: | 8504830 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 0014-2956 |
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| DOI: | 10.1111/j.1432-1033.1993.tb17835.x |