PMID- 28429502
OWN - NLM
STAT- MEDLINE
DCOM- 20180321
LR  - 20180321
IS  - 1440-1681 (Electronic)
IS  - 0305-1870 (Linking)
VI  - 44
IP  - 7
DP  - 2017 Jul
TI  - Involvement of ERK1/2 in Cx43 depression induced by macrophage migration 
      inhibitory factor in atrial myocytes.
PG  - 771-778
LID - 10.1111/1440-1681.12766 [doi]
AB  - Connexin 43 (Cx43) plays an important role in the pathogenesis of atrial 
      fibrillation (AF). The present study sought to investigate the effect of 
      macrophage migration inhibitory factor (MIF), a pleiotropic cytokine, on Cx43 
      expression and activity and determine the intracellular signalling pathways. Cx43 
      protein and mRNA levels were assayed using immunofluorescence, real-time 
      polymerase chain reaction (PCR), and western blot. We found that increased MIF 
      and extracellular regulated protein kinases (ERK) expression was accompanied by a 
      significant reduction in Cx43 protein expression in atrial tissues from patients 
      with AF compared with those with sinus rhythm. In cultured atrium-derived 
      myocytes (HL-1 cells), mouse recombinant-MIF (rMIF, 20 or 40 nmol/L, 24 hours) 
      down-regulated gene and protein expression of Cx43 in a concentration-dependent 
      manner. U0126, a specific inhibitor of mitogen-activated protein kinase kinase 
      (MAPKK) could reverse the decrease in expression of Cx43 protein induced by rMIF. 
      Further studies revealed that rMIF (40 nmol/L, 15, 30, and 45 minutes) was able 
      to stimulate phospho-Erk1/2 (Thr202/Tyr204) production in a time-dependent 
      manner. These results suggest that MIF is involved in the pathogenesis of AF, 
      probably by down-regulating the protein and gene expression of Cx43 via ERK1/2 
      kinase activation. Our findings represent a potential pathogenic mechanism in AF.
CI  - (c) 2017 John Wiley & Sons Australia, Ltd.
FAU - Li, Xin
AU  - Li X
AD  - Department of Cardiology, Guangdong Cardiovascular Institute, Guangzhou, China.
AD  - Guangdong Academy of Medical Sciences, Guangzhou, China.
FAU - Rao, Fang
AU  - Rao F
AUID- ORCID: 0000-0002-1181-2333
AD  - Department of Cardiology, Guangdong Cardiovascular Institute, Guangzhou, China.
AD  - Guangdong Academy of Medical Sciences, Guangzhou, China.
AD  - Research Center of Medical Sciences, Guangdong General Hospital, Guangzhou, 
      China.
FAU - Deng, Chun-Yu
AU  - Deng CY
AD  - Department of Cardiology, Guangdong Cardiovascular Institute, Guangzhou, China.
AD  - Guangdong Academy of Medical Sciences, Guangzhou, China.
AD  - Research Center of Medical Sciences, Guangdong General Hospital, Guangzhou, 
      China.
FAU - Wei, Wei
AU  - Wei W
AD  - Department of Cardiology, Guangdong Cardiovascular Institute, Guangzhou, China.
AD  - Guangdong Academy of Medical Sciences, Guangzhou, China.
FAU - Liu, Fang-Zhou
AU  - Liu FZ
AD  - Department of Cardiology, Guangdong Cardiovascular Institute, Guangzhou, China.
AD  - Guangdong Academy of Medical Sciences, Guangzhou, China.
FAU - Yang, Hui
AU  - Yang H
AD  - Guangdong Academy of Medical Sciences, Guangzhou, China.
AD  - Research Center of Medical Sciences, Guangdong General Hospital, Guangzhou, 
      China.
FAU - Wang, Zhao-Yu
AU  - Wang ZY
AD  - Department of Cardiology, Guangdong Cardiovascular Institute, Guangzhou, China.
AD  - Guangdong Academy of Medical Sciences, Guangzhou, China.
FAU - Kuang, Su-Juan
AU  - Kuang SJ
AD  - Guangdong Academy of Medical Sciences, Guangzhou, China.
AD  - Research Center of Medical Sciences, Guangdong General Hospital, Guangzhou, 
      China.
FAU - Chen, Xiao-Yan
AU  - Chen XY
AD  - Guangdong Academy of Medical Sciences, Guangzhou, China.
AD  - Research Center of Medical Sciences, Guangdong General Hospital, Guangzhou, 
      China.
FAU - Xue, Yu-Mei
AU  - Xue YM
AD  - Department of Cardiology, Guangdong Cardiovascular Institute, Guangzhou, China.
AD  - Guangdong Academy of Medical Sciences, Guangzhou, China.
FAU - Wu, Shu-Lin
AU  - Wu SL
AUID- ORCID: 0000-0002-6378-2009
AD  - Department of Cardiology, Guangdong Cardiovascular Institute, Guangzhou, China.
AD  - Guangdong Academy of Medical Sciences, Guangzhou, China.
AD  - Research Center of Medical Sciences, Guangdong General Hospital, Guangzhou, 
      China.
LA  - eng
PT  - Journal Article
PL  - Australia
TA  - Clin Exp Pharmacol Physiol
JT  - Clinical and experimental pharmacology & physiology
JID - 0425076
RN  - 0 (Connexin 43)
RN  - 0 (Macrophage Migration-Inhibitory Factors)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Atrial Fibrillation/genetics/metabolism/pathology
MH  - Connexin 43/genetics/*metabolism
MH  - Female
MH  - Gene Expression Regulation, Enzymologic/drug effects
MH  - Heart Atria/*cytology/pathology
MH  - Humans
MH  - Macrophage Migration-Inhibitory Factors/*metabolism/pharmacology
MH  - Male
MH  - Mice
MH  - Middle Aged
MH  - Mitogen-Activated Protein Kinase 1/*metabolism
MH  - Mitogen-Activated Protein Kinase 3/*metabolism
MH  - Myocytes, Cardiac/cytology/*metabolism/pathology
MH  - Protein Kinase Inhibitors/pharmacology
MH  - RNA, Messenger/genetics/metabolism
MH  - Signal Transduction/drug effects
MH  - Sinoatrial Node/drug effects/physiology/physiopathology
OTO - NOTNLM
OT  - ERK1/2
OT  - atrial fibrillation
OT  - connexin 43
OT  - macrophage migration inhibitory factor
EDAT- 2017/04/22 06:00
MHDA- 2018/03/22 06:00
CRDT- 2017/04/22 06:00
PHST- 2016/11/22 00:00 [received]
PHST- 2017/03/19 00:00 [revised]
PHST- 2017/03/31 00:00 [accepted]
PHST- 2017/04/22 06:00 [pubmed]
PHST- 2018/03/22 06:00 [medline]
PHST- 2017/04/22 06:00 [entrez]
AID - 10.1111/1440-1681.12766 [doi]
PST - ppublish
SO  - Clin Exp Pharmacol Physiol. 2017 Jul;44(7):771-778. doi: 10.1111/1440-1681.12766.