PMID- 18243130
OWN - NLM
STAT- MEDLINE
DCOM- 20080321
LR  - 20211203
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 368
IP  - 2
DP  - 2008 Apr 4
TI  - Inhibitory crosstalk between ERK and AMPK in the growth and proliferation of 
      cardiac fibroblasts.
PG  - 402-7
LID - 10.1016/j.bbrc.2008.01.099 [doi]
AB  - Extracellular signal-regulated kinase (ERK) is one of the key protein kinases 
      that regulate the growth and proliferation in cardiac fibroblasts (CFs). As an 
      energy sensor of cellular metabolism, AMP-activated protein kinase (AMPK) is 
      found recently to be involved in myocardial remodeling. In this study, we 
      investigated the crosstalk between ERK and AMPK in the growth and proliferation 
      of CFs. In neonatal rat cardiac fibroblasts (NRCFs), we found that serum 
      significantly inhibited basal AMPK phosphorylation between 10min and 24h and also 
      partially inhibited AMPK phosphorylation by AMPK activator, 
      5-aminoimidazole-4-carboxamide-ribonucleoside (AICAR). Furthermore, ERK inhibitor 
      could greatly reverse the inhibition of AMPK by serum. Conversely, activation of 
      AMPK by AICAR also showed a significant inhibition of basal and serum-induced ERK 
      phosphorylation but it showed a delayed and steadfast inhibition which appeared 
      after 60min and lasted until 12h. Moreover, inhibition of ERK could repress the 
      activation of p70S6K, an important kinase in cardiac proliferation, and AICAR 
      could also inhibit p70S6K phosphorylation. In addition, under both serum and 
      serum-free medium, AICAR significantly inhibited the DNA synthesis and cell 
      numbers, and reduced cells at S phase. In conclusion, AMPK activation with AICAR 
      inhibited growth and proliferation in cardiac fibroblasts, which involved 
      inhibitory interactions between ERK and AMPK. This is the first report that AMPK 
      could be a target of ERK in growth factors-induced proliferation, which may give 
      a new mechanism that growth factors utilize in their promotion of proliferation 
      in cardiac fibroblasts.
FAU - Du, Jianhai
AU  - Du J
AD  - Institute of Vascular Medicine, Peking University Third Hospital and Key 
      Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing 
      100083, PR China.
FAU - Guan, Tongju
AU  - Guan T
FAU - Zhang, Hui
AU  - Zhang H
FAU - Xia, Yi
AU  - Xia Y
FAU - Liu, Fei
AU  - Liu F
FAU - Zhang, Youyi
AU  - Zhang Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080201
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.3 (AMP-Activated Protein Kinase Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinase Kinases
MH  - Animals
MH  - Animals, Newborn
MH  - Cell Enlargement
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Extracellular Signal-Regulated MAP Kinases/*metabolism
MH  - Fibroblasts/*cytology/*physiology
MH  - Myocytes, Cardiac/*cytology/*physiology
MH  - Protein Kinases/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/*physiology
EDAT- 2008/02/05 09:00
MHDA- 2008/03/22 09:00
CRDT- 2008/02/05 09:00
PHST- 2007/12/31 00:00 [received]
PHST- 2008/01/19 00:00 [accepted]
PHST- 2008/02/05 09:00 [pubmed]
PHST- 2008/03/22 09:00 [medline]
PHST- 2008/02/05 09:00 [entrez]
AID - S0006-291X(08)00154-X [pii]
AID - 10.1016/j.bbrc.2008.01.099 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2008 Apr 4;368(2):402-7. doi: 
      10.1016/j.bbrc.2008.01.099. Epub 2008 Feb 1.