Nuclear lactate dehydrogenase modulates histone modification in human hepatocytes

被引：34

作者：

Castonguay, Zachary ^{[1
]}

Auger, Christopher ^{[1
]}

Thomas, Sean C. ^{[1
]}

Chahma, M'hamed ^{[1
]}

Appanna, Vasu D. ^{[1
]}

机构：

[1] Laurentian Univ, Dept Chem & Biochem, Sudbury, ON P3E 2C6, Canada

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2014年 / 454卷 / 01期

关键词：

Metabolism; Epigenetics; Lactate dehydrogenase; Sirtuin; Oxidative stress; SIRT1; METABOLISM; INHIBITION; PATHWAY; INACTIVATION; NICOTINAMIDE;

D O I：

10.1016/j.bbrc.2014.10.071

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：

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.

引用

页码：172 / 177

页数：6

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