Protective effect of erythropoietin against ketamine-induced apoptosis in cultured rat cortical neurons: Involvement of PI3K/Akt and GSK-3 beta pathway |
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Authors: | You Shang Yan Wu Shanglong Yao Xiaojing Wang Dan Feng Wenqiong Yang |
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Institution: | (1) Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China;(2) Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;(3) Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;(4) Xuzhou Medical College, Xuzhou, China;(5) Department of Neurology, Dongfeng Hospital, Shiyan, China |
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Abstract: | Erythropoietin (EPO) prevents neuronal cell death through the activation of cell survival signals and the inhibition of apoptotic
signals in models of neurodegenerative diseases. Here we investigated the neuroprotective effect of EPO in ketamine-induced
neurotoxicity in primary cortical neurons. EPO in combination with ketamine greatly increased the cell viability and reduced
the number of TUNEL-positive cells. To elucidate a possible mechanism by which EPO exerts its neuroprotective effect, we investigated
the phosphoinositide3-kinase pathway using LY294002. The neuroprotection of EPO was prevented by LY294002. Immunoblotting
revealed that EPO induced the phosphorylation/activation of Akt and phosphorylation/inactivation of glycogen synthase kinase-3beta
(GSK-3β). Moreover, the caspase-3-like activity was increased by addition of ketamine, and decreased by administration of
ketamine with EPO. Decreased caspase-3-like activity by administration of ketamine with EPO was restored by LY294002. Our
results suggest that PI3K/Akt and GSK-3β pathway are involved in the neuroprotective effect of EPO.
You Shang and Yan Wu have contributed equally to this work. |
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Keywords: | Erythropoietin Ketamine Cortical neurons Neuroprotection Akt GSK-3β Caspase-3 |
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