Inhibition of glutamate dehydrogenase and insulin secretion by KHG26377 does not involve ADP-ribosylation by SIRT4 or deacetylation by SIRT3
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We investigated the mechanisms involved in KHG26377 regulation of glutamate dehydrogenase (GDH) activity, focusing on the roles of SIRT4 and SIRT3. Intraperitoneal injection of mice with KHG26377 reduced GDH activity with concomitant repression of glucose-induced insulin secretion. Consistent with their known functions, SIRT4 ribosylated GDH and reduced its activity, and SIRT3 deacetylated GDH, increasing its activity. However, KHG26377 did not affect SIRT4-mediated ADP-ribosylation/inhibition or SIRT3-mediated deacetylation/activation of GDH. KHG26377 had no effect on SIRT4 protein levels,and did not alter total GDH, acetylated GDH, or SIRT3 protein levels in pancreatic mitochondrial lysates. These results suggest that the mechanism by which KHG26377 inhibits GDH activity and insulin secretion does not involve ADP-ribosylation of GDH by SIRT4 or deacetylation of GDH by SIRT3. [BMB Reports 2012; 45(8): 458-463]
Abstract
We investigated the mechanisms involved in KHG26377 regulation of glutamate dehydrogenase (GDH) activity, focusing on the roles of SIRT4 and SIRT3. Intraperitoneal injection of mice with KHG26377 reduced GDH activity with concomitant repression of glucose-induced insulin secretion. Consistent with their known functions, SIRT4 ribosylated GDH and reduced its activity, and SIRT3 deacetylated GDH, increasing its activity. However, KHG26377 did not affect SIRT4-mediated ADP-ribosylation/inhibition or SIRT3-mediated deacetylation/activation of GDH. KHG26377 had no effect on SIRT4 protein levels,and did not alter total GDH, acetylated GDH, or SIRT3 protein levels in pancreatic mitochondrial lysates. These results suggest that the mechanism by which KHG26377 inhibits GDH activity and insulin secretion does not involve ADP-ribosylation of GDH by SIRT4 or deacetylation of GDH by SIRT3. [BMB Reports 2012; 45(8): 458-463]
참고문헌 (29)
- Katagiri, M., "Reappraisal of the20th-century version of amino acid metabolism", Biochem.Biophys. Res. Commun., 312, pp.205~208 (2003)
- Sener, A., "L-Leucine and a nonmetabolized analogue activate pancreatic islet glutamate dehydrogenase", Nature, 288, pp.187~189 (1980)
- Høy, M. H., "Increase in cellular glutamate levels stimulates exocytosis in pancreatic β-cells", FEBS Lett., 531, pp.199~203 (2002)
- Anno, T., "Overexpression of constitutively activated glutamatedehydrogenase induces insulin secretion through enhancedglutamate oxidation", Am. J. Physiol. Endocrinol.Metab., 286, pp.E280~E285 (2004)
- Carobbio, S., "Insulin secretion profiles are modified by overexpression of glutamate dehydrogenase in pancreatic islets", Diabetologia, 47, pp.266~276 (2004)
- Carobbio, S., "Deletion of glutamate dehydrogenase in β-Cells abolishes part of the insulin secretory response not required for glucose homeostasis", J. Biol. Chem., 284, pp.921~929 (2009)
- Bryla, J., "Regulation of the glutamate dehydrogenase activity in rat islets of Langerhans and its consequence on insulin release", Metabolism, 43, pp.1187~1195 (1994)
- Stanley, C. A., "Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene", N. Engl. J. Med., 338, pp.1352~1357 (1998)
- Yorifuji, T., "Hyperinsulinism-hyperammonemia syndrome caused by mutant glutamate dehydrogenase accompanied by novel enzyme kinetics", Hum. Genet., 104, pp.476~479 (1999)
- MacMullen, C., "Hyperinsulinism", hyperammonemia syndrome in children with regulatory mutations in the inhibitory guanosine triphosphate-binding domain of glutamate dehydrogenase, 2001, pp.86, 1782~1787
- Smith, T. J., "Structures of bovine glutamate dehydrogenase complexes elucidate the mechanism of purine regulation", J. Mol. Biol., 307, pp.707~720 (2001)
- Li, C., "Green tea polyphenols modulated insulin secretion by inhibition glutamate dehydrogenase", J. Biol. Chem., 281, pp.10214~10221 (2006)
- Herrero-Yraola, A., "Regulation of glutamate dehydrogenase by reversible ADP-ribosylation in mitochondria", EMBO J., 20, pp.2404~2412 (2001)
- Zolkiewska, A., "Molecular characterization of NAD: arginine ADP-ribosyltransferase from rabbit skeletal muscle", Proc. Natl. Acad. Sci. U.S.A., 89, pp.11352~11356 (1992)
- Jorcke, D., "Enzymic, cysteine-specific ADP-ribosylation in bovine liver mitochondria", Biochem. J., 332, pp.189~193 (1998)
- Masmoudi, A., "ADP-ribosyl transferase and NAD glycohydrolase activities in rat liver mitochondria", Biochemistry, 26, pp.1965~1969 (1987)
- Frei, B., "Mono(ADP-ribosylation) in rat liver mitochondria", Biochemistry, 27, pp.529~535 (1988)
- Haigis, M. C., "SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic β cells", Cell, 126, pp.941~954 (2006)
- Ahuja, N., "Regulation of insulin secretion by SIRT4, a mitochondrial ADP-ribosyltransferase", J. Biol. Chem., 282, pp.33583~33592 (2007)
- Lombard, D. B., "Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation", Mol. Cell. Biol., 27, pp.8807~8814 (2007)
- Schlicker, C., "Substrates and regulation mechanisms for the human mitochondrial sirtuins Sirt3 and Sirt5", J. Mol. Biol., 382, pp.790~801 (2008)
- Seung-Ju Yang, "Inhibitory effects of KHG26377 on glutamate dehydrogenase activity in cultured islets", BMB Reports, 43(4), pp.245~249 (2010), 생화학분자생물학회
- Cho, S. -W., "Two soluble forms of glutamate dehydrogenase isoproteins from bovine brain", Eur. J. Biochem., 233, pp.340~346 (1995)
- Choi, S. Y., "Different antigenic reactivities of bovine brain glutamate dehydrogenase isoproteins", J. Neurochem., 72, pp.2162~2169 (1999)
- Choi, M. M., "Identification of ADP-ribosylation site in human glutamate dehydrogenase isozymes", FEBS LETTERS, 579, pp.4125~4130 (2005), ELSEVIER SCIENCE BV
- Yang, S. J., "Regulatory effects of 5'-deoxypyridoxal on glutamate dehydrogenase activity and insulin secretion in pancreatic islets", Biochimie, 85, pp.581~586 (2003)
- Argmann, C., "Insulin secretion: SIRT4 gets in on the act", Cell, 126, pp.837~839 (2006)
- Kim, S. C., "Substrate and functional diversity of lysine acetylation revealed by a proteomics survey", MOLECULAR CELL, 23(4), pp.607~618 (2006), CELL PRESS
- Onyango, P., "SIRT3, a human SIR2 homologue, is an NAD-dependent deacetylase localized to mitochondria", Proc. Natl. Acad. Sci. U.S.A., 99, pp.13653~13658 (2002)
