Overexpression of SIRT5 confirms its involvement in deacetylation and activation of carbamoyl phosphate synthetase 1

被引：106

作者：

Ogura, Masahito ^{[1
]}

Nakamura, Yasuhiko ^{[1
]}

Tanaka, Daisuke ^{[1
]}

Zhuang, Xiaotong ^{[1
]}

Fujita, Yoshihito ^{[1
]}

Obara, Akio ^{[1
]}

Hamasaki, Akihiro ^{[1
]}

Hosokawa, Masaya ^{[1
]}

Inagaki, Nobuya ^{[1
]}

机构：

[1] Kyoto Univ, Grad Sch Med, Dept Diabet & Clin Nutr, Sakyo Ku, Kyoto 6068507, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2010年 / 393卷 / 01期

关键词：

SIRT5; Mitochondria; Urea cycle; Liver; CALORIE RESTRICTION; UREA CYCLE; EXPRESSION; LONGEVITY; PATHWAY; INHIBITION; MECHANISMS; CITRULLINE; PROTEINS; COMPLEX;

D O I：

10.1016/j.bbrc.2010.01.081

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

SIR2 protein, an NAD-dependent deacetylase, is localized to nucleus and is involved in life span extension by calorie restriction in yeast. In mammals, among the seven SIR2 homologues (SIRT1-7), SIRT3, 4, and 5 are localized to mitochondria. As SIRT5 mRNA levels in liver are increased by fasting, the physiological role of SIRT5 was investigated in liver of SIRT5-overexpressing transgenic (SIRT5 Tg) mice. We identified carbamoyl phosphate synthetase I (CPS1), a key enzyme of the urea cycle that catalyzes condensation of ammonia with bicarbonate to form carbamoyl phosphate, as a target of SIRT5 by two-dimensional electrophoresis comparing mitochondrial proteins in livers of SIRT5 Tg and wild-type mice. CPS1 protein was more deacetylated and activated in liver of SIRT5 Tg mice than in wild-type. In addition, urea production was upregulated in hepatocytes of SIRT5 Tg mice. These results agree with those of a previous study using SIRT5 knockout (KO) mice. Because ammonia generated during fasting is toxic, SIRT5 protein might play a protective role by converting ammonia to non-toxic urea through deacetylation and activation of CPS1. (C) 2010 Elsevier Inc. All rights reserved.

引用

页码：73 / 78

页数：6

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