Retinoic acid-induced gene expression of tissue transglutaminase via protein kinase C-dependent pathway in mouse peritoneal macrophages.
Culture of mouse resident peritoneal macrophages with retinoic acid resulted in increased expression of the tissue transglutaminase gene as revealed by increases in the maximal velocity of the enzyme reaction in the cytosol and in the enzyme mRNA level. Protein kinase C-activating phorbol esters and okadaic acid, both of which were without effect on the enzyme induction by themselves, enhanced the retinoic acid-induced gene expression, which was in turn inhibited partially by pertussis toxin and totally by inhibitors of protein kinase C in either the presence or absence of phorbol esters. Retinoic acid was more effective in the "conditioned" medium, in which macrophages had been cultured for a time longer than 4 h, than in the "fresh" medium. The retinoic acid induction of transglutaminase was accompanied by increased phosphatidylinositol turnover and phosphatidic acid generation, which were efficiently suppressed by prior exposure of cells to pertussis toxin. It is likely that certain autocrine factor(s) liberated during culture of macrophages may afford conditions favorable for retinoic acid-induced gene expression, presumably via pertussis toxin-sensitive G protein-mediated phosphoinositide metabolism leading to activation of protein kinase C.
Ishii
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Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, University of Tokyo.
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D000818:Animals; D002478:Cells, Cultured; D004789:Enzyme Activation; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006728:Hormones / Q000502:physiology; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D037342:Pertussis Toxin; D010716:Phosphatidylinositols / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology*; D012016:Reference Values; D011503:Transglutaminases / Q000235:genetics*; D014212:Tretinoin / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D006728:Hormones; D010716:Phosphatidylinositols; D010743:Phospholipids; D010566:Virulence Factors, Bordetella; D014212:Tretinoin; D011503:Transglutaminases; D037342:Pertussis Toxin; D011493:Protein Kinase C