Picklo Matthew J
Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota, School of Medicine and Health Sciences, 501 N. Columbia Road, Grand Forks, ND 58203-9037, USA.
Biochem Biophys Res Commun. 2008 Nov 21;376(3):615-9. doi: 10.1016/j.bbrc.2008.09.039. Epub 2008 Sep 18.
The acetylation of the epsilon-amino group of lysine to form N-acetyl lysine (N-AcLys)-modified proteins regulates the activity of metabolic proteins. Because of the multiple effects of ethanol upon hepatic metabolism, it was hypothesized that ethanol exposure increases the hepatic content of N-AcLys-modified proteins. To test this hypothesis, rats or mice were exposed to ethanol using a liquid diet regimen. Content of N-AcLys-modified proteins was elevated more than 5-fold after 6 weeks of ethanol exposure and persisted after ethanol withdrawal. Use of CYP2E1-knockout mice demonstrated that ethanol-induced acetylation was not dependent solely on CYP2E1 expression. The mitochondrial content of N-AcLys-modified proteins was elevated almost 5-fold following 6 weeks of ethanol exposure. Mitochondrial content of the deacetylase Sirt3 was unchanged by 6 weeks of ethanol exposure. These data indicate ethanol intoxication changes the acetylation status of, and likely the activity of, multiple mitochondrial proteins.
赖氨酸ε-氨基乙酰化形成N-乙酰赖氨酸（N-AcLys）修饰的蛋白质可调节代谢蛋白的活性。由于乙醇对肝脏代谢有多种影响，因此推测乙醇暴露会增加肝脏中N-AcLys修饰蛋白的含量。为了验证这一假设，使用液体饮食方案让大鼠或小鼠暴露于乙醇中。乙醇暴露6周后，N-AcLys修饰蛋白的含量升高了5倍以上，且在乙醇戒断后仍持续存在。使用CYP2E1基因敲除小鼠表明，乙醇诱导的乙酰化并不完全依赖于CYP2E1的表达。乙醇暴露6周后，线粒体中N-AcLys修饰蛋白的含量几乎升高了5倍。乙醇暴露6周后，去乙酰化酶Sirt3的线粒体含量没有变化。这些数据表明，乙醇中毒会改变多种线粒体蛋白的乙酰化状态，并可能改变其活性。
