PMID- 34278478
OWN - NLM
STAT- MEDLINE
DCOM- 20211214
LR  - 20211214
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Print)
IS  - 1791-2997 (Linking)
VI  - 24
IP  - 3
DP  - 2021 Sep
TI  - Interactions between the ERK1/2 signaling pathway and PCAF play a key role in 
      PE‑induced cardiomyocyte hypertrophy.
LID - 636 [pii]
LID - 10.3892/mmr.2021.12275 [doi]
AB  - Cardiomyocyte hypertrophy is a compensatory phase of chronic heart failure that 
      is induced by the activation of multiple signaling pathways. The extracellular 
      signal‑regulated protein kinase (ERK) signaling pathway is an important regulator 
      of cardiomyocyte hypertrophy. In our previous study, it was demonstrated that 
      phenylephrine (PE)‑induced cardiomyocyte hypertrophy involves the 
      hyperacetylation of histone H3K9ac by P300/CBP‑associated factor (PCAF). However, 
      the upstream signaling pathway has yet to be fully identified. In the present 
      study, the role of the extracellular signal‑regulated protein kinase (ERK)1/2 
      signaling pathway in PE‑induced cardiomyocyte hypertrophy was investigated. The 
      mice cardiomyocyte hypertrophy model was successfully established by treating 
      cells with PE in vitro. The results showed that phospho‑(p‑)ERK1/2 interacted 
      with PCAF and modified the pattern of histone H3K9ac acetylation. An ERK 
      inhibitor (U0126) and/or a histone acetylase inhibitor (anacardic acid; AA) 
      attenuated the overexpression of phospho‑ERK1/2 and H3K9ac hyperacetylation by 
      inhibiting the expression of PCAF in PE‑induced cardiomyocyte hypertrophy. 
      Moreover, U0126 and/or AA could attenuate the overexpression of several biomarker 
      genes related to cardiac hypertrophy (myocyte enhancer factor 2C, atrial 
      natriuretic peptide, brain natriuretic peptide and beta‑myosin heavy chain) and 
      prevented cardiomyocyte hypertrophy. These results revealed a novel mechanism in 
      that AA protects against PE‑induced cardiomyocyte hypertrophy in mice via the 
      ERK1/2 signaling pathway, and by modifying the acetylation of H3K9ac. These 
      findings may assist in the development of novel methods for preventing and 
      treating hypertrophic cardiomyopathy.
FAU - Mao, Qian
AU  - Mao Q
AD  - Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi, 
      Guizhou 563000, P.R. China.
FAU - Wu, Shuqi
AU  - Wu S
AD  - Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi, 
      Guizhou 563000, P.R. China.
FAU - Peng, Chang
AU  - Peng C
AD  - Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi, 
      Guizhou 563000, P.R. China.
FAU - Peng, Bohui
AU  - Peng B
AD  - Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi, 
      Guizhou 563000, P.R. China.
FAU - Luo, Xiaomei
AU  - Luo X
AD  - Department of Physiology, School of Basic Medical Sciences, Zunyi Medical 
      University, Zunyi, Guizhou 563000, P.R. China.
FAU - Huang, Lixin
AU  - Huang L
AD  - Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi, 
      Guizhou 563000, P.R. China.
FAU - Zhang, Huanting
AU  - Zhang H
AD  - Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi, 
      Guizhou 563000, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20210719
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Anacardic Acids)
RN  - 0 (Butadienes)
RN  - 0 (Histones)
RN  - 0 (MEF2 Transcription Factors)
RN  - 0 (Nitriles)
RN  - 0 (U 0126)
RN  - 18654-18-7 (anacardic acid)
RN  - 1WS297W6MV (Phenylephrine)
RN  - EC 2.3.1.48 (Histone Acetyltransferases)
RN  - EC 2.3.1.48 (p300-CBP Transcription Factors)
RN  - EC 2.3.1.48 (p300-CBP-associated factor)
SB  - IM
MH  - Acetylation
MH  - Anacardic Acids
MH  - Animals
MH  - Butadienes
MH  - Cardiomegaly/metabolism
MH  - Cell Survival
MH  - Disease Models, Animal
MH  - Female
MH  - Histone Acetyltransferases
MH  - Histones/metabolism
MH  - MAP Kinase Signaling System/*physiology
MH  - MEF2 Transcription Factors
MH  - Male
MH  - Mice
MH  - Myocytes, Cardiac/*metabolism
MH  - Nitriles
MH  - Phenylephrine/*pharmacology
MH  - Signal Transduction/drug effects
MH  - p300-CBP Transcription Factors/*metabolism
PMC - PMC8281443
OTO - NOTNLM
OT  - ERK‑signaling pathway
OT  - anacardic acid
OT  - cardiomyocyte hypertrophy
OT  - histone acetylation
COIS- The authors declare that they have no competing interests.
EDAT- 2021/07/20 06:00
MHDA- 2021/12/15 06:00
PMCR- 2021/07/06
CRDT- 2021/07/19 06:11
PHST- 2020/11/25 00:00 [received]
PHST- 2021/06/23 00:00 [accepted]
PHST- 2021/07/19 06:11 [entrez]
PHST- 2021/07/20 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/07/06 00:00 [pmc-release]
AID - 636 [pii]
AID - MMR-0-0-12275 [pii]
AID - 10.3892/mmr.2021.12275 [doi]
PST - ppublish
SO  - Mol Med Rep. 2021 Sep;24(3):636. doi: 10.3892/mmr.2021.12275. Epub 2021 Jul 19.