PMID- 29278652
OWN - NLM
STAT- MEDLINE
DCOM- 20200617
LR  - 20211204
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Linking)
VI  - 120
IP  - 4
DP  - 2019 Apr
TI  - Poly(ADP-ribose) polymerase 1 induces cardiac fibrosis by mediating mammalian 
      target of rapamycin activity.
PG  - 4813-4826
LID - 10.1002/jcb.26649 [doi]
AB  - Cardiac fibrosis is involved in nearly all forms of heart diseases and is 
      characterized by excessive deposition of extracellular matrix proteins by cardiac 
      fibroblasts (CFs). We and others have reported the possibility of 
      poly(ADP-ribose) polymerase 1 (PARP1), the founding subtype of the PARPs enzyme 
      family, as a novel therapeutic target of heart diseases. The cardiac fibrotic 
      induction of mammalian target of rapamycin (mTOR) is mainly due to collagen 
      expression, Smad3- and p53/JNK-mediated apoptosis. However, the possible link 
      between PARP1 and mTOR in the progression of cardiac fibrosis remains unclear. In 
      this study, PARP1 protein expression, and the activity of mTOR and its three 
      target substrates (p70 ribosomal S6 Kinase 1, eukaryotic initiation factor 
      4E--binding protein 1, and UNC-51-like kinase 1) were augmented; meanwhile, the 
      nicotinamide adenine dinucleotide (NAD) content was significantly reduced in the 
      process of cardiac fibrosis in vivo and in vitro. Sprague-Dawley rats were 
      intraperitoneally injected with 3-aminobenzamide (3AB) (20 mg/kg/d; a 
      well-established PARP1 inhibitor) or rapamycin (Rapa; 1 mg/kg/d; used for mTOR 
      inhibition) 7 days after abdominal aortic constriction (AAC) surgery for 6 weeks. 
      Pretreatment of 3AB or Rapa both relieved AAC-caused cardiac fibrosis and heart 
      dysfunction. Overexpression of PARP1 with adenovirus carrying PARP1 gene 
      specifically transduced into the hearts via intramyocardial multipoint injection 
      caused similar myocardial damage. In CFs, preincubation with PARP1 or mTOR 
      inhibitors all blocked TGF-beta1 induced cardiac fibrosis. PARP1 overexpression 
      evoked cardiac fibrosis, which could be antagonized by mTOR inhibitors or NAD 
      supplementation in CFs. These results provide novel and compelling evidence that 
      PARP1 exacerbated cardiac fibrosis, which was partially attributed to 
      NAD-dependent activation of mTOR.
CI  - (c) 2019 Wiley Periodicals, Inc.
FAU - Sun, Shuya
AU  - Sun S
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
FAU - Hu, Yuehuai
AU  - Hu Y
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
FAU - Zheng, Qiyao
AU  - Zheng Q
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
FAU - Guo, Zhen
AU  - Guo Z
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
FAU - Sun, Duanping
AU  - Sun D
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
FAU - Chen, Shaorui
AU  - Chen S
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
FAU - Zhang, Yiqiang
AU  - Zhang Y
AD  - Division of Cardiology, Department of Medicine, Center for Cardiovascular 
      Biology, Institute for Stem Cell and Regenerative Medicine, University of 
      Washington, Seattle, Washington.
FAU - Liu, Peiqing
AU  - Liu P
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
FAU - Lu, Jing
AU  - Lu J
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
FAU - Jiang, Jianmin
AU  - Jiang J
AUID- ORCID: 0000-0002-3271-1662
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190111
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - EC 2.4.2.30 (Parp1 protein, rat)
RN  - EC 2.4.2.30 (Poly (ADP-Ribose) Polymerase-1)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adenoviridae
MH  - Animals
MH  - Fibrosis
MH  - Heart Diseases/*enzymology/genetics/pathology
MH  - Male
MH  - Myocardium/*enzymology/pathology
MH  - Poly (ADP-Ribose) Polymerase-1/genetics/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - TOR Serine-Threonine Kinases/genetics/*metabolism
MH  - Transduction, Genetic
OTO - NOTNLM
OT  - NAD
OT  - cardiac fibrosis
OT  - mammalian target of rapamycin (mTOR)
OT  - poly(ADP-ribose) polymerase 1 (PARP1)
OT  - transforming growth factor-beta1 (TGF-beta1)
EDAT- 2017/12/27 06:00
MHDA- 2020/06/18 06:00
CRDT- 2017/12/27 06:00
PHST- 2017/10/13 00:00 [received]
PHST- 2017/12/20 00:00 [accepted]
PHST- 2017/12/27 06:00 [pubmed]
PHST- 2020/06/18 06:00 [medline]
PHST- 2017/12/27 06:00 [entrez]
AID - 10.1002/jcb.26649 [doi]
PST - ppublish
SO  - J Cell Biochem. 2019 Apr;120(4):4813-4826. doi: 10.1002/jcb.26649. Epub 2019 Jan 
      11.