PMID- 22166638
OWN - NLM
STAT- MEDLINE
DCOM- 20120425
LR  - 20191210
IS  - 2542-5641 (Electronic)
IS  - 0366-6999 (Linking)
VI  - 123
IP  - 24
DP  - 2010 Dec
TI  - Neuregulin-1 preconditioning protects the heart against ischemia/reperfusion 
      injury through a PI3K/Akt-dependent mechanism.
PG  - 3597-604
AB  - BACKGROUND: Neuregulin-1 (NRG-1), the ligand of the myocardial ErbB receptor, is 
      a protein mediator with regulatory actions in the heart. This study investigated 
      whether NRG-1 preconditioning has protective effects on myocardial 
      ischemia/reperfusion (I/R) injury and its potential mechanism. METHODS: We worked 
      with an in vivo rat model with induced myocardial ischemia (45 minutes) followed 
      by reperfusion (3 hours). NRG-1 message was detected in the heart using RT-PCR 
      and the protein levels of NRG-1 and ErbB4 were detected by Western blotting 
      analysis. Infarct size was assessed using the staining agent triphenyltetrazolium 
      chloride and cardiac function was continuously monitored. The levels of creatine 
      kinase and lactate dehydrogenase in plasma were analyzed to assess the degree of 
      cardiac injury. The extent of cardiac apoptosis was evaluated by terminal 
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and by 
      Western blotting analysis of cleaved caspase-3. We examined the phosphorylation 
      of Akt in the myocardium and the effect of PI3K/Akt inhibition on NRG-1-induced 
      cardioprotection. RESULTS: Transcription and expression of NRG-1 and 
      phosphorylation of its ErbB4 receptor were significantly upregulated in the I/R 
      hearts. NRG-1 pretreatment reduced the infarct size following cardiac I/R in a 
      concentration-dependent manner with an optimal concentration of 4 microg/kg in vivo. 
      NRG-1 pretreatment with 4 microg/kg, i.v. markedly reduced the plasma creatine kinase 
      and lactate dehydrogenase levels. Pretreatment with NRG-1 also significantly 
      reduced the percentage of TUNEL positive myocytes and the level of cleaved 
      caspase-3 in the I/R hearts. Pretreatment with NRG-1 significantly increased 
      phosphorylation of Akt following I/R. Furthermore, the cardioprotective effect 
      limiting the infarct size that was induced by NRG-1 was abolished by 
      co-administration of the PI3K inhibitor LY294002. CONCLUSIONS: The concentration 
      of NRG-1, a new autacoid, was rapidly upregulated after myocardial I/R. NRG-1 
      preconditioning has cardioprotective effects against I/R injury through a 
      PI3K/Akt-dependent mechanism in vivo.
FAU - Fang, Shan-Juan
AU  - Fang SJ
AD  - Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, 
      Beijing 100029, China.
FAU - Wu, Xue-Si
AU  - Wu XS
FAU - Han, Zhi-Hong
AU  - Han ZH
FAU - Zhang, Xiao-Xia
AU  - Zhang XX
FAU - Wang, Chun-Mei
AU  - Wang CM
FAU - Li, Xin-Yan
AU  - Li XY
FAU - Lu, Ling-Qiao
AU  - Lu LQ
FAU - Zhang, Jing-Lan
AU  - Zhang JL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Chin Med J (Engl)
JT  - Chinese medical journal
JID - 7513795
RN  - 0 (Neuregulin-1)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Erbb4 protein, rat)
RN  - EC 2.7.10.1 (Receptor, ErbB-4)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Caspase 3/metabolism
MH  - Dose-Response Relationship, Drug
MH  - ErbB Receptors/analysis
MH  - *Ischemic Preconditioning, Myocardial
MH  - L-Lactate Dehydrogenase/blood
MH  - Male
MH  - Myocardial Reperfusion Injury/*prevention & control
MH  - Neuregulin-1/analysis/*pharmacology
MH  - Phosphatidylinositol 3-Kinases/*physiology
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-akt/*physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, ErbB-4
EDAT- 2011/12/15 06:00
MHDA- 2012/04/26 06:00
CRDT- 2011/12/15 06:00
PHST- 2011/12/15 06:00 [entrez]
PHST- 2011/12/15 06:00 [pubmed]
PHST- 2012/04/26 06:00 [medline]
PST - ppublish
SO  - Chin Med J (Engl). 2010 Dec;123(24):3597-604.