Alcohol alters hepatic FoxO1, p53, and mitochondrial SIRT5 deacetylation function
Alcohol alters hepatic FoxO1, p53, and mitochondrial SIRT5 deacetylation function
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DOI：
10.1016/j.bbrc.2008.06.006
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发表时间：
2008-08-22
影响因子：
3.1
通讯作者：
DeCarli, Leonore M.
中科院分区：
文献类型：
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作者：
Lieber, Charles S.;Leo, Maria Anna;DeCarli, Leonore M.
慢性饮酒影响NAD依赖性cleacetylase Sirtuis 1（SIRT 1）和过氧化物酶体增殖物激活受体-γ辅激活因子1 α（PGC-1 α）的基因表达。我们的目的是验证它也改变了叉头（FoxO 1）和p53转录因子蛋白，这在肝脏对氧化应激的反应中至关重要，并通过SIRT 1的脱乙酰化能力进行调节。因此，大鼠成对喂食含Lieber-DeCarli酒精的液体饲料28天。酒精增加肝脏FoxO 1（p = 0.003）和p53（p = 0.001）的mRNA表达，而相应的蛋白质水平保持不变。然而，磷酸化FoxO 1和磷酸化Akt（蛋白激酶）均因饮酒而降低（分别为p = 0.04和p = 0.02），而肝脏p53被发现过度乙酰化（p = 0.017）。此外，线粒体SIRT 5减少（p = 0.0025），PGC-1 α高度乙酰化（p = 0.027），确立了它们在蛋白质修饰中的作用。因此，酒精消耗通过翻译后蛋白质修饰破坏核-线粒体相互作用，这通过新发现的SIRT 5减少而有助于线粒体生物发生的改变。(C)2008年爱思唯尔公司All rights reserved.
Chronic alcohol consumption affects the gene expression of a NAD-depenclent cleacetylase Sirtuis 1 (SIRT1) and the peroxisome proliferator-activated receptor-gamma coactivator1 alpha (PGC-1 alpha). Our aim was to verify that it also alters the forkhead (FoxO1) and p53 transcription factor proteins, critical in the hepatic response to oxidative stress and regulated by SIRT1 through its deacetylating capacity. Accordingly, rats were pair-fed the Lieber-DeCarli alcohol-containing liquid diets for 28 days. Alcohol increased hepatic mRNA expression of FoxO1 (p = 0.003) and p53 (p = 0.001) while corresponding protein levels remained unchanged. However phospho-FoxO1 and phospho-Akt (protein kinase) were both decreased by alcohol consumption (p = 0.04 and p = 0.02, respectively) while hepatic p53 was found hyperacetylated (p = 0.017). Furthermore, mitochondrial SIRT5 was reduced (p = 0.0025), and PGC-1 alpha hyperacetylated (p = 0.027), establishing their role in protein modification. Thus, alcohol consumption disrupts nuclear-mitochondrial interactions by post-translation protein modifications, which contribute to alteration of mitochondrial biogenesis through the newly discovered reduction of SIRT5. (C) 2008 Elsevier Inc. All rights reserved.