KGH26377 通过抑制谷氨酸脱氢酶和胰岛素分泌，不涉及 SIRT4 的 ADP-核糖基化或 SIRT3 的去乙酰化。
Inhibition of glutamate dehydrogenase and insulin secretion by KHG26377 does not involve ADP-ribosylation by SIRT4 or deacetylation by SIRT3.
机构信息
Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea.
出版信息
BMB Rep. 2012 Aug;45(8):458-63. doi: 10.5483/bmbrep.2012.45.8.040.
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.
我们研究了 KHG26377 调节谷氨酸脱氢酶 (GDH) 活性的机制，重点研究了 SIRT4 和 SIRT3 的作用。腹腔注射 KHG26377 可降低 GDH 活性，同时抑制葡萄糖诱导的胰岛素分泌。与它们已知的功能一致，SIRT4 使 GDH 发生核糖基化并降低其活性，SIRT3 使 GDH 去乙酰化，从而增加其活性。然而，KHG26377 不影响 SIRT4 介导的 ADP-核糖基化/抑制作用或 SIRT3 介导的 GDH 去乙酰化/激活作用。KHG26377 对 SIRT4 蛋白水平没有影响，也不改变胰腺线粒体裂解物中的总 GDH、乙酰化 GDH 或 SIRT3 蛋白水平。这些结果表明，KHG26377 抑制 GDH 活性和胰岛素分泌的机制不涉及 SIRT4 对 GDH 的 ADP-核糖基化或 SIRT3 对 GDH 的去乙酰化。
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