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Granulocyte colony stimulating factor directly inhibits myocardial ischemia-reperfusion injury through Akt-endothelial NO synthase pathway.

AbstractOBJECTIVE:
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.
AuthorsKazutaka Ueda, Hiroyuki Takano, Hiroshi Hasegawa, Yuriko Niitsuma, Yingjie Qin, Masashi Ohtsuka, Issei Komuro
JournalArteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 26 Issue 6 Pg. e108-13 (Jun 2006) ISSN: 1524-4636 [Electronic] United States
PMID16574892 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Cardiotonic Agents
  • Granulocyte Colony-Stimulating Factor
  • Nitric Oxide Synthase Type III
  • Proto-Oncogene Proteins c-akt
Topics
  • Animals
  • Cardiotonic Agents (pharmacology)
  • Enzyme Activation
  • Granulocyte Colony-Stimulating Factor (pharmacology)
  • In Vitro Techniques
  • Male
  • Myocardial Infarction (pathology)
  • Myocardial Reperfusion Injury (prevention & control)
  • Myocardium (metabolism)
  • Nitric Oxide Synthase Type III (metabolism)
  • Proto-Oncogene Proteins c-akt (metabolism)
  • Rats
  • Rats, Wistar
  • Signal Transduction

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