Nuclear lactate dehydrogenase modulates histone modification in human hepatocytes
Nuclear lactate dehydrogenase modulates histone modification in human hepatocytes
复制标题
DOI：
10.1016/j.bbrc.2014.10.071
复制
发表时间：
2014-11-07
影响因子：
3.1
通讯作者：
Appanna, Vasu D.
中科院分区：
文献类型：
--
作者：
Castonguay, Zachary;Auger, Christopher;Appanna, Vasu D.
越来越明显的是，细胞核中含有影响遗传转化事件的代谢酶。在这里，我们描述了乳酸脱氢酶（nLDH）的核亚型及其通过控制烟酰胺腺嘌呤二核苷酸（NAD（+））的可用性来协调组蛋白脱乙酰化的能力，烟酰胺腺嘌呤二核苷酸（NAD（+））是sirtuin-1（SIRT1）脱乙酰酶系统的关键成分。随着培养基中过氧化氢（H2O2）的存在，nLDH 的表达增加。在氧化应激下，尽管 SIRT1 水平没有明显变化，但与对照肝细胞相比，nLDH 产生的 NAD(+) 导致组蛋白脱乙酰化增强。当 nLDH 和 SIRT1 共免疫沉淀时，这两种酶之间似乎存在密切关联。 nLDH 通过操纵 NAD(+) 来调节表观遗传修饰的能力揭示了新陈代谢和遗传信息处理之间的复杂联系。 (C) 2014 Elsevier Inc. 保留所有权利。
It is becoming increasingly apparent that the nucleus harbors metabolic enzymes that affect genetic transforming events. Here, we describe a nuclear isoform of lactate dehydrogenase (nLDH) and its ability to orchestrate histone deacetylation by controlling the availability of nicotinamide adenine dinucleotide (NAD(+)), a key ingredient of the sirtuin-1 (SIRT1) deacetylase system. There was an increase in the expression of nLDH concomitant with the presence of hydrogen peroxide (H2O2) in the culture medium. Under oxidative stress, the NAD(+) generated by nLDH resulted in the enhanced deacetylation of histones compared to the control hepatocytes despite no discernable change in the levels of SIRT1. There appeared to be an intimate association between nLDH and SIRT1 as these two enzymes co-immunoprecipitated. The ability of nLDH to regulate epigenetic modifications by manipulating NAD(+) reveals an intricate link between metabolism and the processing of genetic information. (C) 2014 Elsevier Inc. All rights reserved.