دورية أكاديمية
Effects of modulators of protein phosphorylation on heme metabolism in human hepatic cells: induction of delta-aminolevulinic synthase mRNA and protein by okadaic acid.
العنوان: | Effects of modulators of protein phosphorylation on heme metabolism in human hepatic cells: induction of delta-aminolevulinic synthase mRNA and protein by okadaic acid. |
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المؤلفون: | Cable EE; Department of Microbiology and Immunology, Penn State College of Medicine, Hershey, Pennsylvania 17033, USA., Kuhn BR, Isom HC |
المصدر: | DNA and cell biology [DNA Cell Biol] 2002 Apr; Vol. 21 (4), pp. 323-32. |
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: Mary Ann Liebert Country of Publication: United States NLM ID: 9004522 Publication Model: Print Cited Medium: Print ISSN: 1044-5498 (Print) Linking ISSN: 10445498 NLM ISO Abbreviation: DNA Cell Biol Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Larchmont, NY : Mary Ann Liebert Original Publication: [New York, NY] : Mary Ann Liebert, [c1990- |
مواضيع طبية MeSH: | 5-Aminolevulinate Synthetase/*biosynthesis , Heme/*metabolism , Hepatocytes/*metabolism, Cell Line ; Dose-Response Relationship, Drug ; Enzyme Induction/drug effects ; Enzyme Inhibitors/pharmacology ; Humans ; Okadaic Acid/pharmacology ; Phosphorylation ; RNA, Messenger/biosynthesis |
مستخلص: | Effects of modulators of protein phosphorylation on delta-aminolevulinic acid (ALA) synthase and heme oxygenase-1 mRNA were analyzed in the human hepatic cell lines Huh-7 and HepG2 using a quantitative RNase protection assay. Okadaic acid was found to induce ALA synthase mRNA in a concentration-dependent fashion in both Huh-7 and HepG2 cells. The EC(50) for induction of ALA synthase mRNA in Huh-7 cells was 13.5 nM, with maximum increases occurring at okadaic acid concentrations of 25-50 nM. The EC(50) for induction of ALA synthase mRNA in HepG2 cells was 35.5 nM, with maximum increases occurring at okadaic acid concentrations of 50 nM. Concentration-dependent induction of ALA synthase mRNA paralleled the increase in ALA synthase protein. Maximum induction of ALA synthase was observed between 5 and 10 h post-treatment in both cell lines. Induction of ALA synthase mRNA in Huh-7 cells, but not HepG2 cells, was associated with an increase in ALA synthase mRNA stability. Okadaic acid also induced heme oxygenase-1 mRNA in both cell lines, but the magnitude of induction was only twofold, and was rapid and transient. Okadaic acid and phorbol 12-myristate 13-acetate significantly decreased heme-mediated induction of heme oxygenase-1 mRNA in both Huh-7 and HepG2 cells. Wortmannin diminished the heme-mediated induction of heme oxygenase-1 mRNA in HepG2 cells, but not Huh-7 cells. These results report a novel property of okadaic acid to affect heme metabolism in human cell lines. |
معلومات مُعتمدة: | DK53430 United States DK NIDDK NIH HHS; DK54482 United States DK NIDDK NIH HHS |
المشرفين على المادة: | 0 (Enzyme Inhibitors) 0 (RNA, Messenger) 1W21G5Q4N2 (Okadaic Acid) 42VZT0U6YR (Heme) EC 2.3.1.37 (5-Aminolevulinate Synthetase) |
تواريخ الأحداث: | Date Created: 20020604 Date Completed: 20020611 Latest Revision: 20131121 |
رمز التحديث: | 20240627 |
DOI: | 10.1089/104454902753759735 |
PMID: | 12042071 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1044-5498 |
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DOI: | 10.1089/104454902753759735 |