PMID- 30734677
OWN - NLM
STAT- MEDLINE
DCOM- 20191004
LR  - 20211204
IS  - 1875-5666 (Electronic)
IS  - 1566-5240 (Linking)
VI  - 18
IP  - 10
DP  - 2018
TI  - Histone Deacetylase Inhibition Attenuates Cardiomyocyte Hypoxia-Reoxygenation 
      Injury.
PG  - 711-718
LID - 10.2174/1566524019666190208102729 [doi]
AB  - BACKGROUND: Cardiac reperfusion injury can have devastating consequences. Histone 
      deacetylase (HDAC) inhibitors are potent cytoprotective agents, but their role in 
      the prevention of cardiac injury remains ill-defined. OBJECTIVE: We sought to 
      determine the therapeutic potential of HDAC inhibitors in an in vitro model of 
      cardiomyocyte hypoxia-reoxygenation (H/R). METHOD: H9c2 cardiomyocytes were 
      subjected to H/R and treated with various classspecific and pan-HDAC inhibitors 
      in equal concentrations (5microM). Biological activity of inhibitors was determined, 
      as a proxy for concentration adequacy, by Western blot for acetylated histone H3 
      and alpha-tubulin. Cell viability and cytotoxicity were measured by methyl thiazolyl 
      tetrazolium and lactate dehydrogenase assays, respectively. Mechanistic studies 
      were performed to better define the effects of the most effective agent, 
      Tubastatin-A (Tub-A), on the phosphoinositide 3-kinase (PI3K)/mammalian target of 
      rapamycin (mTOR) pathway effectors, and on the degree of autophagy. RESULTS: All 
      inhibitors acetylated well-known target proteins (histone H3 and alpha-tubulin), 
      suggesting that concentrations were adequate to induce a biological effect. 
      Improved cell viability and decreased cell cytotoxicity were noted in 
      cardiomyocytes exposed to Tub-A, whereas the cytoprotective effects of other HDAC 
      inhibitors were inconsistent. Pro-survival mediators in the PI3K/mTOR pathway 
      were up-regulated and the degree of autophagy was significantly attenuated in 
      cells that were treated with Tub-A. CONCLUSION: HDAC inhibitors improve cell 
      viability in a model of cardiomyocyte H/R, with Class IIb inhibition (Tub-A) 
      demonstrating superior cellular-level potency and effectiveness. This effect is, 
      at least in part, related to an increased expression of prosurvival mediators and 
      a decreased degree of autophagy.
CI  - Copyright(c) Bentham Science Publishers; For any queries, please email at 
      epub@benthamscience.net.
FAU - Williams, Aaron M
AU  - Williams AM
AD  - Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan, 
      United States.
FAU - He, Wei
AU  - He W
AD  - Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan, 
      United States.
AD  - Department of Surgery, Zhongda Hospital, School of Medicine, Southeast 
      University, Nanjing, China.
FAU - Li, Yongqing
AU  - Li Y
AD  - Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan, 
      United States.
FAU - Bhatti, Umar F
AU  - Bhatti UF
AD  - Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan, 
      United States.
FAU - Nikolian, Vahagn C
AU  - Nikolian VC
AD  - Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan, 
      United States.
FAU - Chang, Panpan
AU  - Chang P
AD  - Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan, 
      United States.
FAU - Chang, Zhigang
AU  - Chang Z
AD  - Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan, 
      United States.
AD  - Department of Surgical Intensive Care, Beijing Hospital Ministry of Health, 
      Beijing, China.
FAU - Halaweish, Ihab
AU  - Halaweish I
AD  - Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan, 
      United States.
FAU - Liu, Baoling
AU  - Liu B
AD  - Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan, 
      United States.
FAU - Cheng, Xin
AU  - Cheng X
AD  - Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan, 
      United States.
FAU - Alam, Hasan B
AU  - Alam HB
AD  - Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan, 
      United States.
LA  - eng
GR  - R01 GM084127/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - Netherlands
TA  - Curr Mol Med
JT  - Current molecular medicine
JID - 101093076
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Histones)
RN  - 0 (Tubulin)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Acetylation/drug effects
MH  - Animals
MH  - Cell Line
MH  - Histone Deacetylase Inhibitors/*pharmacology
MH  - Histones/metabolism
MH  - Mice
MH  - *Models, Cardiovascular
MH  - Myocardial Reperfusion Injury/drug therapy/*metabolism/pathology
MH  - Myocytes, Cardiac/*metabolism/pathology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Signal Transduction/*drug effects
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Tubulin/metabolism
OTO - NOTNLM
OT  - Histone deacetylase
OT  - cardiac injury
OT  - histone deacetylase inhibitors
OT  - hypoxia-reoxygenation
OT  - ischemia-reperfusion injury.
EDAT- 2019/02/09 06:00
MHDA- 2019/10/08 06:00
CRDT- 2019/02/09 06:00
PHST- 2018/08/30 00:00 [received]
PHST- 2018/12/28 00:00 [revised]
PHST- 2019/01/24 00:00 [accepted]
PHST- 2019/02/09 06:00 [pubmed]
PHST- 2019/10/08 06:00 [medline]
PHST- 2019/02/09 06:00 [entrez]
AID - CMM-EPUB-96503 [pii]
AID - 10.2174/1566524019666190208102729 [doi]
PST - ppublish
SO  - Curr Mol Med. 2018;18(10):711-718. doi: 10.2174/1566524019666190208102729.