PMID- 29613828
OWN - NLM
STAT- MEDLINE
DCOM- 20190208
LR  - 20190503
IS  - 1559-2308 (Electronic)
IS  - 1559-2294 (Print)
IS  - 1559-2294 (Linking)
VI  - 13
IP  - 4
DP  - 2018
TI  - Activation of Class I histone deacetylases contributes to mitochondrial 
      dysfunction in cardiomyocytes with altered complex activities.
PG  - 376-385
LID - 10.1080/15592294.2018.1460032 [doi]
AB  - Histone deacetylases (HDACs) play vital roles in the pathophysiology of heart 
      failure, which is associated with mitochondrial dysfunction. Tumor necrosis 
      factor-alpha (TNF-alpha) contributes to the genesis of heart failure and impairs 
      mitochondria. This study evaluated the role of HDACs in TNF-alpha-induced 
      mitochondrial dysfunction and investigated their therapeutic potential and 
      underlying mechanisms. We measured mitochondrial oxygen consumption rate (OCR) 
      and ATP production using Seahorse XF24 extracellular flux analyzer and 
      bioluminescent assay in control and TNF-alpha (10 ng/ml, 24 h)-treated HL-1 cells 
      with or without HDAC inhibition. TNF-alpha increased Class I and II (but not Class 
      IIa) HDAC activities (assessed by Luminescent) with enhanced expressions of Class 
      I (HDAC1, HDAC2, HDAC3, and HDAC8) but not Class IIb HDAC (HDAC6 and HDAC10) 
      proteins in HL-1 cells. TNF-alpha induced mitochondrial dysfunction with impaired 
      basal, ATP-linked, and maximal respiration, decreased cellular ATP synthesis, and 
      increased mitochondrial superoxide production (measured by MitoSOX red 
      fluorescence), which were rescued by inhibiting HDACs with MPT0E014 (1 muM, a 
      Class I and IIb inhibitor), or MS-275 (1 muM, a Class I inhibitor). MPT0E014 
      reduced TNF-alpha-decreased complex I and II enzyme (but not III or IV) activities 
      (by enzyme activity microplate assays). Our results suggest that Class I HDAC 
      actions contribute to TNF-alpha-induced mitochondrial dysfunction in cardiomyocytes 
      with altered complex I and II enzyme regulation. HDAC inhibition improves 
      dysfunctional mitochondrial bioenergetics with attenuation of TNF-alpha-induced 
      oxidative stress, suggesting the therapeutic potential of HDAC inhibition in 
      cardiac dysfunction.
FAU - Lkhagva, Baigalmaa
AU  - Lkhagva B
AD  - a Graduate Institute of Clinical Medicine, College of Medicine , Taipei Medical 
      University , Taipei , Taiwan.
AD  - b Department of Cardiology, School of Medicine , Mongolian National University of 
      Medical Sciences , Ulaanbaatar , Mongolia.
FAU - Kao, Yu-Hsun
AU  - Kao YH
AD  - a Graduate Institute of Clinical Medicine, College of Medicine , Taipei Medical 
      University , Taipei , Taiwan.
AD  - c Department of Medical Education and Research , Wan Fang Hospital , Taipei 
      Medical University , Taipei , Taiwan.
FAU - Lee, Ting-I
AU  - Lee TI
AD  - d Division of Endocrinology and Metabolism , Department of General Medicine , 
      School of Medicine, College of Medicine , Taipei Medical University , Taipei , 
      Taiwan.
AD  - e Department of Internal Medicine , Wan Fang Hospital , Taipei Medical University 
      , Taipei , Taiwan.
FAU - Lee, Ting-Wei
AU  - Lee TW
AD  - a Graduate Institute of Clinical Medicine, College of Medicine , Taipei Medical 
      University , Taipei , Taiwan.
AD  - f Division of Endocrinology and Metabolism, Department of Internal Medicine , Wan 
      Fang Hospital , Taipei Medical University , Taipei , Taiwan.
FAU - Cheng, Wan-Li
AU  - Cheng WL
AD  - a Graduate Institute of Clinical Medicine, College of Medicine , Taipei Medical 
      University , Taipei , Taiwan.
FAU - Chen, Yi-Jen
AU  - Chen YJ
AD  - a Graduate Institute of Clinical Medicine, College of Medicine , Taipei Medical 
      University , Taipei , Taiwan.
AD  - g Division of Cardiovascular Medicine, Department of Internal Medicine , Wan Fang 
      Hospital , Taipei Medical University , Taipei , Taiwan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180503
PL  - United States
TA  - Epigenetics
JT  - Epigenetics
JID - 101265293
RN  - 0 (3-(1-benzenesulfonyl-1H-indol-5-yl)-N-hydroxyacrylamide)
RN  - 0 (Benzamides)
RN  - 0 (Hydroxamic Acids)
RN  - 0 (Indoles)
RN  - 0 (Pyridines)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 1ZNY4FKK9H (entinostat)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 3.5.1.98 (Histone Deacetylases)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Benzamides/pharmacology
MH  - Cell Line
MH  - Histone Deacetylases/*metabolism
MH  - Hydroxamic Acids/pharmacology
MH  - Indoles/pharmacology
MH  - Mice
MH  - Mitochondria/*drug effects/metabolism
MH  - Myocytes, Cardiac/*cytology/drug effects
MH  - Oxygen Consumption/drug effects
MH  - Pyridines/pharmacology
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - *Up-Regulation/drug effects
PMC - PMC6140820
OTO - NOTNLM
OT  - Mitochondria
OT  - bioenergetics
OT  - histone deacetylase inhibition
EDAT- 2018/04/04 06:00
MHDA- 2019/02/09 06:00
PMCR- 2019/05/03
CRDT- 2018/04/04 06:00
PHST- 2018/04/04 06:00 [pubmed]
PHST- 2019/02/09 06:00 [medline]
PHST- 2018/04/04 06:00 [entrez]
PHST- 2019/05/03 00:00 [pmc-release]
AID - 1460032 [pii]
AID - 10.1080/15592294.2018.1460032 [doi]
PST - ppublish
SO  - Epigenetics. 2018;13(4):376-385. doi: 10.1080/15592294.2018.1460032. Epub 2018 
      May 3.