TAILIEUCHUNG - Báo cáo Y học: Control of p70 ribosomal protein S6 kinase and acetyl-CoA carboxylase by AMP-activated protein kinase and protein phosphatases in isolated hepatocytes

Certain amino acids, like glutamine and leucine, induce an anabolic response in liver. They activate p70 ribosomal protein S6 kinase (p70S6K) and acetyl-CoA carboxylase (ACC) involved in protein and fatty acids synthesis, respectively. In contrast, the AMP-activated protein kinase (AMPK), which senses the energy state of the cell and becomes activated under metabolic stress, inactivates by phosphorylation key enzymes in biosynthetic pathways thereby conserving ATP. In this paper, we studied the effect of AMPK activation and of protein phosphatase inhibitors, on the amino-acid-induced activation of p70S6K and ACC in hepatocytes in suspension. AMPK was activated under anoxic conditions or by. | Eur. J. Biochem. 269 3751-3759 2002 FEBS 2002 doi Control of p70 ribosomal protein S6 kinase and acetyl-CoA carboxylase by AMP-activated protein kinase and protein phosphatases in isolated hepatocytes Ulrike Krause Luc Bertrand and Louis Hue Hormone and Metabolic Research Unit Christian de Duve International Institute of Cellular and Molecular Pathology and University of Louvain Medical School Brussels Belgium Certain amino acids like glutamine and leucine induce an anabolic response in liver. They activate p70 ribosomal protein S6 kinase p70S6K add acytyl-CoA carboxylase ACC invvlved in proinin and fatty acids synthesis respectively. In contrast the AMP-activated protein kinase AMPK which senses the energy state of the cell and becomes activated under metabolic stress inactivates by phosphorylation key enzymes in biosynthetic pathways thereby conserving ATP. In this paper we studied the effect of AMPK activation and of protein phosphatase inhibitors on the amino-acid-induced activation of p70S6K and ACC in hepatocytes in suspension. AMPK was activated under anoxic conditions or by incubation with 5-aminoimidazole-4-carboxyamide ribonucleoside AICAr or oligomycin an inhibitor of mitochondrial oxidative phosphorylation. Incubation of hepatocytes with amino acids activated p70S6K via multiple phosphorylation. It also activated ACC by a phosphatase-dependent mechanism but did not modify AMPK activation. Conversely the amino-acid-induced activation of both ACC and p70S6K was blocked or reversed when AMPK was activated. This AMPK activation increased Ser79 phosphorylation in ACC but decreased Thr389 phosphorylation in p70S6K. Protein phosphatase inhibitors prevented p70S6K activation when added prior to the incubation with amino acids whereas they enhanced p70S6K activation when added after the preincubation with amino acids. It is concluded that a AMPK blocks amino-acid-induced activation of ACC and p70S6K directly by phosphorylating .

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