PMID- 36745702
OWN - NLM
STAT- MEDLINE
DCOM- 20230330
LR  - 20230516
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Print)
IS  - 0021-9541 (Linking)
VI  - 238
IP  - 3
DP  - 2023 Mar
TI  - Deacetylase-dependent and -independent role of HDAC3 in cardiomyopathy.
PG  - 647-658
LID - 10.1002/jcp.30957 [doi]
AB  - Cardiomyopathy is a common disease of cardiac muscle that negatively affects 
      cardiac function. HDAC3 commonly functions as corepressor by removing acetyl 
      moieties from histone tails. However, a deacetylase-independent role of HDAC3 has 
      also been described. Cardiac deletion of HDAC3 causes reduced cardiac 
      contractility accompanied by lipid accumulation, but the molecular function of 
      HDAC3 in cardiomyopathy remains unknown. We have used powerful genetic tools in 
      Drosophila to investigate the enzymatic and nonenzymatic roles of HDAC3 in 
      cardiomyopathy. Using the Drosophila heart model, we showed that cardiac-specific 
      HDAC3 knockdown (KD) leads to prolonged systoles and reduced cardiac 
      contractility. Immunohistochemistry revealed structural abnormalities 
      characterized by myofiber disruption in HDAC3 KD hearts. Cardiac-specific HDAC3 
      KD showed increased levels of whole-body triglycerides and increased fibrosis. 
      The introduction of deacetylase-dead HDAC3 mutant in HDAC3 KD background showed 
      comparable results with wild-type HDAC3 in aspects of contractility and 
      Pericardin deposition. However, deacetylase-dead HDAC3 mutants failed to improve 
      triglyceride accumulation. Our data indicate that HDAC3 plays a 
      deacetylase-independent role in maintaining cardiac contractility and preventing 
      Pericardin deposition as well as a deacetylase-dependent role to maintain 
      triglyceride homeostasis.
CI  - (c) 2023 Wiley Periodicals LLC.
FAU - Ren, Jieyu
AU  - Ren J
AD  - Department of Biochemistry and Molecular Biology, College of Hengyang Medical, 
      University of South China, Hengyang, China.
FAU - Zeng, Qun
AU  - Zeng Q
AD  - Department of Biochemistry and Molecular Biology, College of Hengyang Medical, 
      University of South China, Hengyang, China.
FAU - Wu, Hongmei
AU  - Wu H
AD  - Department of Biochemistry and Molecular Biology, College of Hengyang Medical, 
      University of South China, Hengyang, China.
FAU - Liu, Xuewen
AU  - Liu X
AD  - Department of Biochemistry and Molecular Biology, College of Hengyang Medical, 
      University of South China, Hengyang, China.
FAU - Guida, Maria C
AU  - Guida MC
AD  - Development Aging and Regeneration Program, Sanford Burnham Prebys Medical 
      Discovery Institute, La Jolla, California, USA.
FAU - Huang, Wen
AU  - Huang W
AD  - Center for Medical Genetics, School of Life Sciences, Central South University, 
      Changsha, Hunan, China.
FAU - Zhai, Yiyuan
AU  - Zhai Y
AD  - Department of Biochemistry and Molecular Biology, College of Hengyang Medical, 
      University of South China, Hengyang, China.
FAU - Li, Junjie
AU  - Li J
AD  - Department of Biochemistry and Molecular Biology, College of Hengyang Medical, 
      University of South China, Hengyang, China.
FAU - Ocorr, Karen
AU  - Ocorr K
AD  - Development Aging and Regeneration Program, Sanford Burnham Prebys Medical 
      Discovery Institute, La Jolla, California, USA.
FAU - Bodmer, Rolf
AU  - Bodmer R
AD  - Development Aging and Regeneration Program, Sanford Burnham Prebys Medical 
      Discovery Institute, La Jolla, California, USA.
FAU - Tang, Min
AU  - Tang M
AD  - Department of Biochemistry and Molecular Biology, College of Hengyang Medical, 
      University of South China, Hengyang, China.
LA  - eng
GR  - R01 HL054732/HL/NHLBI NIH HHS/United States
GR  - R21 AG075446/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230206
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Drosophila Proteins)
RN  - EC 3.5.1.98 (Hdac3 protein, Drosophila)
RN  - EC 3.5.1.98 (Histone Deacetylases)
RN  - 0 (Histones)
RN  - 0 (Prc protein, Drosophila)
RN  - 0 (Triglycerides)
SB  - IM
MH  - Animals
MH  - *Cardiomyopathies/enzymology/genetics/metabolism/physiopathology
MH  - *Disease Models, Animal
MH  - *Drosophila melanogaster/enzymology/genetics/metabolism
MH  - *Drosophila Proteins/deficiency/genetics/metabolism
MH  - Gene Knockdown Techniques
MH  - Heart/physiology
MH  - *Histone Deacetylases/deficiency/genetics/metabolism
MH  - Histones/chemistry/metabolism
MH  - Myocardium/metabolism
MH  - Triglycerides/metabolism
MH  - Homeostasis
PMC - PMC10152801
MID - NIHMS1882545
OTO - NOTNLM
OT  - Drosophila
OT  - Pericardin
OT  - cardiac contractility
OT  - cardiomyopathy
OT  - deacetylase
OT  - fibrosis
OT  - triglycerides
EDAT- 2023/02/07 06:00
MHDA- 2023/03/22 06:00
PMCR- 2023/05/02
CRDT- 2023/02/06 14:07
PHST- 2022/12/14 00:00 [revised]
PHST- 2022/07/31 00:00 [received]
PHST- 2023/01/11 00:00 [accepted]
PHST- 2023/02/07 06:00 [pubmed]
PHST- 2023/03/22 06:00 [medline]
PHST- 2023/02/06 14:07 [entrez]
PHST- 2023/05/02 00:00 [pmc-release]
AID - 10.1002/jcp.30957 [doi]
PST - ppublish
SO  - J Cell Physiol. 2023 Mar;238(3):647-658. doi: 10.1002/jcp.30957. Epub 2023 Feb 6.