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Postconditioning effect of granulocyte colony-stimulating factor is mediated through activation of risk pathway and opening of the mitochondrial KATP channels.
- Source :
-
American Journal of Physiology: Heart & Circulatory Physiology . Oct2010, Vol. 299 Issue 4, pH1174-H1182. 9p. 1 Diagram, 1 Graph. - Publication Year :
- 2010
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Abstract
- Granulocyte-colony-stimulating factor(G-CSF) has been reported to improve cardiac function after myocardial infarction (MI). However, whether postinfarct acute effect of G-CSF is mediated through the same signaling pathways as those of ischemic postconditioning is still unclear. We examined the postinfarct acute effect of G-CSF on myocardial infarct size and its precise molecular mechanism. Japanese white rabbits underwent 30 min of ischemia and 48 h of reperfusion. Rabbits were intravenously injected 10 μg/kg of G-CSF (G-CSF group), saline (control group) immediately after reperfusion. The wortmannin+G-CSF, PD98059+G-CSF, Nω-nitro-L-arginine methyl ester (L-NAME) + G-CSF, and 5-HD+G-CSF groups were respectively injected with wortmannin(0.6mg/kg), PD98059(0.3mg/kg), L-NAME(10mg/kg) and 5-HD(5mg/kg), 5 min before G-CSF administration. Myocardial infarct size was calculated as a percentage of the risk area of the left ventricle. Western blot analysis was performed to examine the signals such as Akt, ERK, eNOS, p70S6K and GSK3β in the ischemic myocardium after 48 hours of reperfusion. The infarct size was significantly smaller in the G-CSF group (26.7±2.7%) than in the control group (42.3±4.6%). The infarct size-reducing effect of G-CSF was completely blocked by wortmannin(44.7±4.8%), PD98059(38.3±3.9%), L-NAME (42.1±4.2%) and 5-HD (42.5±1.7%). Wortmannin, PD98059, L-NAME or 5HD alone did not affect the infarct size. Western blotting showed higher myocardial expression of phospho-Akt, phospho-ERK, phosho-eNOS, phosho-p70S6K and phosho-GSK3β at 10 min and 48 hours after reperfusion in the G-CSF group than in the control group. In conclusion, postreperfusion G-CSF administration reduces myocardial infarct size via activation of PI3K-Akt and ERK prosurvival signaling pathways and their down stream targets eNOS, p70S6K, GSK3β and mitochondrial KATP channels. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03636135
- Volume :
- 299
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- American Journal of Physiology: Heart & Circulatory Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 53993855
- Full Text :
- https://doi.org/10.1152/ajpheart.00116.2010