PMID- 29932238
OWN - NLM
STAT- MEDLINE
DCOM- 20191008
LR  - 20200812
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Linking)
VI  - 119
IP  - 9
DP  - 2018 Sep
TI  - ERbeta targets ZAK and attenuates cellular hypertrophy via SUMO-1 modification in 
      H9c2 cells.
PG  - 7855-7864
LID - 10.1002/jcb.27199 [doi]
AB  - Aberrant expression of leucine zipper- and sterile a motif-containing kinase 
      (ZAK) observed in pathological human myocardial tissue is associated with the 
      progression and elevation of hypertrophy. Our previous reports have correlated 
      high levels of estrogen (E2) and abundant estrogen receptor (ER) alpha with a low 
      incidence of pathological cardiac-hypertrophy and heart failure in the 
      premenopause female population. However, the effect of elevated ERbeta expression is 
      not well known yet. Therefore, in this study, we have analyzed the 
      cardioprotective effects and mechanisms of E2 and/or ERbeta against ZAK 
      overexpression-induced cellular hypertrophy. We have used transient transfection 
      to overexpress ERbeta into the ZAK tet-on H9c2 cells that harbor the 
      doxycycline-inducible ZAK plasmid. The results show that ZAK overexpression in 
      H9c2 cells resulted in hypertrophic effects, which was correlated with the 
      upregulation of p-JNK and p-p38 MAPKs and their downstream transcription factors 
      c-Jun and GATA-4. However, ERbeta and E2 with ERbeta overexpressions totally suppressed 
      the effects of ZAK overexpression and inhibited the levels of p-JNK, p-p38, 
      c-Jun, and GATA-4 effectively. Our results further reveal that ERbeta directly binds 
      with ZAK under normal conditions; however, ZAK overexpression reduced the 
      association of ZAK-ERbeta. Interestingly, increase in ERbeta and E2 along with ERbeta 
      overexpression both enhanced the binding strengths of ERbeta and ZAK and reduced the 
      ZAK protein level. ERbeta overexpression also suppressed the E3 ligase-casitas 
      B-lineage lymphoma (CBL) and attenuated CBL-phosphoinositide 3-kinase (PI3K) 
      protein association to prevent PI3K protein degradation. Moreover, ERbeta and/or E2 
      blocked ZAK nuclear translocation via the inhibition of small ubiquitin-like 
      modi fi er (SUMO)-1 modification. Taken together, our results further suggest that 
      ERbeta overexpression strongly suppresses ZAK-induced cellular hypertrophy and 
      myocardial damage.
CI  - (c) 2018 Wiley Periodicals, Inc.
FAU - Pai, Peiying
AU  - Pai P
AD  - Division of Cardiology, China Medical University Hospital, Taichung, Taiwan.
FAU - Shibu, Marthandam Asokan
AU  - Shibu MA
AD  - Graduate Institute of Basic Medical Science, China Medical University, Taichung, 
      Taiwan.
FAU - Chang, Ruey-Lin
AU  - Chang RL
AD  - College of Chinese Medicine, School of Post-Baccalaureate Chinese Medicine, China 
      Medical University, Taichung, Taiwan.
FAU - Yang, Jaw-Ji
AU  - Yang JJ
AD  - Institute of Medicine, School of Dentistry, Chung-Shan Medical University, 
      Taichung, Taiwan.
FAU - Su, Chia-Chi
AU  - Su CC
AD  - Graduate Institute of Basic Medical Science, China Medical University, Taichung, 
      Taiwan.
FAU - Lai, Chao-Hung
AU  - Lai CH
AD  - Division of Cardiology, Department of Internal Medicine, Taichung Armed Force 
      General Hospital, Taichung, Taiwan.
FAU - Liao, Hung-En
AU  - Liao HE
AD  - Department of Healthcare Administration, Asia University, Taichung, Taiwan.
FAU - Viswanadha, Vijaya Padma
AU  - Viswanadha VP
AD  - Department of Biotechnology, Bharathiar University, Coimbatore, India.
FAU - Kuo, Wei-Wen
AU  - Kuo WW
AD  - Department of Biological Science and Technology, China Medical University, 
      Taichung, Taiwan.
FAU - Huang, Chih-Yang
AU  - Huang CY
AUID- ORCID: 0000-0003-2347-0411
AD  - Graduate Institute of Basic Medical Science, China Medical University, Taichung, 
      Taiwan.
AD  - Department of Biotechnology, Asia University, Taichung, Taiwan.
AD  - Graduate Institute of Chinese Medical Science, China Medical University, 
      Taichung, Taiwan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180622
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (Estrogen Receptor beta)
RN  - 0 (Estrogens)
RN  - 0 (SUMO-1 Protein)
RN  - EC 2.3.2.27 (Proto-Oncogene Proteins c-cbl)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.- (Map3k20 protein, rat)
SB  - IM
MH  - Animals
MH  - Cell Enlargement
MH  - Cell Line
MH  - Estrogen Receptor beta/*genetics/metabolism
MH  - Estrogens/pharmacology
MH  - Gene Expression Regulation
MH  - Myoblasts, Cardiac/*cytology/drug effects/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Protein Kinases/genetics/*metabolism
MH  - Proto-Oncogene Proteins c-cbl
MH  - Rats
MH  - SUMO-1 Protein/*metabolism
OTO - NOTNLM
OT  - 17beta-estradiol
OT  - MAP3 kinase
OT  - ZAK
OT  - estrogen receptor
OT  - hypertrophy
EDAT- 2018/06/23 06:00
MHDA- 2019/10/09 06:00
CRDT- 2018/06/23 06:00
PHST- 2017/11/01 00:00 [received]
PHST- 2018/05/24 00:00 [accepted]
PHST- 2018/06/23 06:00 [pubmed]
PHST- 2019/10/09 06:00 [medline]
PHST- 2018/06/23 06:00 [entrez]
AID - 10.1002/jcb.27199 [doi]
PST - ppublish
SO  - J Cell Biochem. 2018 Sep;119(9):7855-7864. doi: 10.1002/jcb.27199. Epub 2018 Jun 
      22.