Abstract
Volatile anesthetic ischemic postconditioning reduces infarct size following ischemia/reperfusion. Whether phosphorylation of protein kinase B (PKB/Akt) and glycogen synthase kinase 3 beta (GSK3β) is causal for cardioprotection by postconditioning is controversial. We therefore investigated the impact of PKB/Akt and GSK3β in isolated perfused rat hearts subjected to 40 min of ischemia followed by 1 h of reperfusion. 2.0% sevoflurane (1.0 minimum alveolar concentration) was administered at the onset of reperfusion in 15 min as postconditioning. Western blot analysis was used to determine phosphorylation of PKB/Akt and its downstream target GSK3β after 1 h of reperfusion. Mitochondrial and cytosolic content of cytochrome C checked by western blot served as a marker for mitochondrial permeability transition pore opening. Sevoflurane postconditioning significantly improved functional cardiac recovery and decreased infarct size in isolated rat hearts. Compared with unprotected hearts, sevoflurane postconditioning-induced phosphorylation of PKB/Akt and GSK3β were significantly increased. Increase of cytochrome C in mitochondria and decrease of it in cytosol is significant when compared with unprotected ones which have reversal effects on cytochrome C. The current study presents evidence that sevoflurane-induced cardioprotection at the onset of reperfusion are partly through activation of PKB/Akt and GSK3β.
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Acknowledgments
The authors would like to thank Dr. Lv Na-Qiang and Dr. Chang Xin for their technical assistance. This work was supported with the grants from Ph.D. Programs Foundation of Ministry of Education of China (No.20070023012).
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The current study presents evidence that activation of PKB/Akt and GSK3β produced by sevoflurane postconditioning in isolated rat hearts takes a crucial role in attenuating ischemia–reperfusion injury.
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Fang, NX., Yao, YT., Shi, CX. et al. Attenuation of ischemia–reperfusion injury by sevoflurane postconditioning involves protein kinase B and glycogen synthase kinase 3 beta activation in isolated rat hearts. Mol Biol Rep 37, 3763–3769 (2010). https://doi.org/10.1007/s11033-010-0030-5
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DOI: https://doi.org/10.1007/s11033-010-0030-5