Triiodothyronine-induced accumulations of malic enzyme, fatty acid synthase, acetyl-coenzyme A carboxylase, and their mRNAs are blocked by protein kinase inhibitors. Transcription is the affected step

• Published in: The Journal of biological chemistry Vol. 266; no. 26; pp. 17459 - 17466
• Main Authors: SWIERCZYNSKI, J, MICHELL, D. A, REINHOLD, D. S, SALATI, L. M, STAPLETON, S. R, KLAUTKY, S. A, STRUVE, A. E, GOODRIDGE, A. G
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Biochemistry and Molecular Biology 15.09.1991
• Subjects: Acetyl-CoA Carboxylase - genetics; Acetyl-CoA Carboxylase - metabolism; Alkaloids - pharmacology; Animals; Biological and medical sciences; Cell physiology; Cells, Cultured; Chick Embryo; Fatty Acid Synthases - genetics; Fatty Acid Synthases - metabolism; Fundamental and applied biological sciences. Psychology; Hormonal regulation; Isoquinolines - pharmacology; Liver - enzymology; Malate Dehydrogenase - genetics; Malate Dehydrogenase - metabolism; Metallothionein - genetics; Molecular and cellular biology; Protein Kinase Inhibitors; RNA, Messenger - metabolism; Staurosporine; Transcription, Genetic - drug effects; Triiodothyronine - antagonists & inhibitors; Triiodothyronine - pharmacology; Cell culture; Embryo; Transcription; Enzyme; Aminoacid derivative hormone; Enzyme inhibitor; Vertebrata; Acetyl-CoA carboxylase; Hepatocyte; Protein kinase; Hormonal regulation; Thyroid hormone; Fatty acid synthase; Chicken; Triiodothyronine; Inhibition; Aves
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(19)47395-X

Addition of triiodothyronine (T3) to chick-embryo hepatocytes in culture causes increased accumulations of malic enzyme, fatty acid synthase, acetyl-CoA carboxylase and their mRNAs. H-8 and other protein kinase inhibitors inhibited the T3-induced accumulations of these lipogenic enzymes and their mRNAs but had no effect on the activities of 6-phosphogluconate dehydrogenase and isocitrate dehydrogenase, enzymes not induced by T3 in chick-embryo hepatocytes. H-8 also had no effect on the activities of malic enzyme, fatty acid synthase, and acetyl-CoA carboxylase in hepatocytes not treated with T3. Synthesis of soluble protein, levels of mRNAs for beta-actin and glyceraldehyde-3-phosphate dehydrogenase, and induction of metallothionein mRNA by Zn2+ were unaffected by H-8 at concentrations that inhibited the T3-induced accumulation of lipogenic enzymes and their mRNAs. H-8 inhibited T3-induced transcription of the genes for both malic enzyme and fatty acid synthase but had little effect on transcription of the beta-actin or glyceraldehyde-3-phosphate dehydrogenase genes or on total RNA synthesis in isolated nuclei. H-8 also had no effect on binding of T3 to its nuclear receptor. In isolated nuclei, H-8 inhibited phosphorylation of total protein by 15-20%. Phosphorylation of only one major protein was consistently and substantially inhibited, indicating that the effect of H-8 was selective. These results suggest that on-going protein phosphorylation is required specifically for stimulation of transcription of the lipogenic genes by T3.