Document Detail

Granulocyte colony stimulating factor directly inhibits myocardial ischemia-reperfusion injury through Akt-endothelial NO synthase pathway.
MedLine Citation:
PMID:  16574892     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Granulocyte colony stimulating factor (G-CSF) has been reported recently to prevent cardiac remodeling and dysfunction after acute myocardial infarction through signal transducer and activator of transcription 3 (STAT3). In this study, we examined acute effects of G-CSF on the heart against ischemia-reperfusion injury. METHODS AND RESULTS: Rat hearts were subjected to global 35-minute ischemia and 120-minute reperfusion in Langendorff system with or without G-CSF (300 ng/mL). G-CSF administration was started at the onset of reperfusion. Triphenyltetrazolium chloride staining revealed that G-CSF markedly reduced the infarct size. G-CSF strongly activated Janus kinase 2 (Jak2), STAT3, extracellular signal-regulated kinase (ERK), Akt, and endothelial NO synthase (NOS) in the hearts subjected to ischemia followed by 15-minute reperfusion. The G-CSF-induced reduction in infarct size was abolished by inhibitors of phosphatidylinositol 3-kinase, Jak2, and NOS but not of mitogen-activated protein kinase kinase (MEK). CONCLUSIONS: These results suggest that G-CSF acts directly on the myocardium during ischemia-reperfusion injury and has acute nongenomic cardioprotective effects through the Akt-endothelial NOS pathway.
Kazutaka Ueda; Hiroyuki Takano; Hiroshi Hasegawa; Yuriko Niitsuma; Yingjie Qin; Masashi Ohtsuka; Issei Komuro
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-03-30
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  26     ISSN:  1524-4636     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-05-19     Completed Date:  2006-06-16     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e108-13     Citation Subset:  IM    
Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Japan.
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MeSH Terms
Cardiotonic Agents / pharmacology*
Enzyme Activation
Granulocyte Colony-Stimulating Factor / pharmacology*
Myocardial Infarction / pathology
Myocardial Reperfusion Injury / prevention & control*
Myocardium / metabolism*
Nitric Oxide Synthase Type III / metabolism*
Proto-Oncogene Proteins c-akt / metabolism*
Rats, Wistar
Signal Transduction
Reg. No./Substance:
0/Cardiotonic Agents; 143011-72-7/Granulocyte Colony-Stimulating Factor; EC Oxide Synthase Type III; EC Proteins c-akt

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