The inhibition of lactate dehydrogenase A hinders the transcription of histone 2B gene independently from the block of aerobic glycolysis

被引:8
作者
Brighenti, Elisa [1 ]
Carnicelli, Domenica [1 ]
Brigotti, Maurizio [1 ]
Fiume, Luigi [1 ]
机构
[1] Univ Bologna, Dept Expt Diagnost & Specialty Med, Bologna, Italy
关键词
Anti-proliferative agents; Nuclear LDHA inhibition; Histone 2B gene transcription inhibitors; Oxamic acid; GSK; 2837808A; MOLECULAR CHARACTERIZATION; DEFICIENCY; EXPRESSION; ACID; BINDING; PROTEIN; GROWTH; CELLS; LEAD; DNA;
D O I
10.1016/j.bbrc.2017.02.119
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
Most cancer cells use aerobic glycolysis to fuel their growth and many efforts are made to selectively block this metabolic pathway in cancer cells by inhibiting lactate dehydrogenase A (LDHA). However, LDHA is a moonlighting protein which exerts functions also in the nucleus as a factor associated to transcriptional complexes. Here we found that two small molecules which inhibit the enzymatic activity of LDHA hinder the transcription of histone 2B gene independently from the block of aerobic glycolysis. Moreover, we observed that silencing this gene reduces cell replication, hence suggesting that the inhibition of LDHA can also affect the proliferation of normal non-glycolysing dividing cells. (C) 2017 Elsevier Inc. All rights reserved.
引用
收藏
页码:742 / 745
页数:4
相关论文
共 24 条
[1]  
Barker SB, 1941, J BIOL CHEM, V138, P535
[2]  
Billiard J, 2013, CANCER METAB, V1, DOI 10.1186/2049-3002-1-19
[3]   EFFECTS OF SUBUNIT INTERACTIONS ON ACTIVITY OF LACTATE-DEHYDROGENASE STUDIED IN IMMOBILIZED ENZYME-SYSTEMS [J].
CHAN, WWC ;
MOSBACH, K .
BIOCHEMISTRY, 1976, 15 (19) :4215-4222
[4]   Histone 2B (H2B) expression is confined to a proper NAD+/NADH redox status [J].
Dai, Ru-Ping ;
Yu, Fa-Xing ;
Goh, Shuang-Ru ;
Chng, Hsiao-Wee ;
Tan, Ya-Li ;
Fu, Jian-Lin ;
Zheng, Lei ;
Luo, Yan .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (40) :26894-26901
[5]   Selective inhibition of rRNA transcription downregulates E2F-1: a new p53-independent mechanism linking cell growth to cell proliferation [J].
Donati, Giulio ;
Brighenti, Elisa ;
Vici, Manuela ;
Mazzini, Giuliano ;
Trere, Davide ;
Montanaro, Lorenzo ;
Derenzini, Massimo .
JOURNAL OF CELL SCIENCE, 2011, 124 (17) :3017-3028
[6]  
EAGLE H, 1958, J BIOL CHEM, V233, P551
[7]   Identification of 3,6-disubstituted dihydropyrones as inhibitors of human lactate dehydrogenase [J].
Fauber, Benjamin P. ;
Dragovich, Peter S. ;
Chen, Jinhua ;
Corson, Laura B. ;
Ding, Charles Z. ;
Eigenbrot, Charles ;
Labadie, Sharada ;
Malek, Shiva ;
Peterson, David ;
Purkey, Hans E. ;
Robarge, Kirk ;
Sideris, Steve ;
Ultsch, Mark ;
Wei, BinQing ;
Yen, Ivana ;
Yue, Qin ;
Zhou, Aihe .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2014, 24 (24) :5683-5687
[8]   INHIBITION OF AEROBIC GLYCOLYSIS IN YOSHIDA ASCITES HEPATOMA BY TARTRONIC ACID [J].
FIUME, L .
NATURE, 1960, 187 (4739) :792-793
[9]  
Fiume L, 2014, FUTURE MED CHEM, V6, P429, DOI [10.4155/FMC.13.206, 10.4155/fmc.13.206]
[10]   Galloflavin prevents the binding of lactate dehydrogenase A to single stranded DNA and inhibits RNA synthesis in cultured cells [J].
Fiume, Luigi ;
Vettraino, Marina ;
Camicelli, Domenica ;
Arfilli, Valentina ;
Di Stefano, Giuseppina ;
Brigotti, Maurizio .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2013, 430 (02) :466-469