Melatonin Induces Akt Phosphorylation through Melatonin Receptor- and PI3K-Dependent Pathways in Primary Astrocytes

다국어 초록 (Multilingual Abstract)

Melatonin has been reported to protect neurons from a variety of neurotoxicity. However, the
underlying mechanism by which melatonin exerts its neuroprotective property has not yet been clearly
understood. We previously demonstrated that melatonin protected kainic acid-induced neuronal cell
death in mouse hippocampus, accompanied by sustained activation of Akt, a critical mediator of
neuronal survival. To further elucidate the neuroprotective action of melatonin, we examined in the
present study the causal mechanism how Akt signaling pathway is regulated by melatonin in a rat
primary astrocyte culture model. Melatonin resulted in increased astrocytic Akt phosphorylation, which
was significantly decreased with wortmannin, a specific inhibitor of PI3K, suggesting that activation
of Akt by melatonin is mediated through the PI3K-Akt signaling pathway. Furthermore, increased
Akt activation was also significantly decreased with luzindole, a non-selective melatonin receptor
antagonist. As downstream signaling pathway of Akt activation, increased levels of CREB
phoshorylation and GDNF expression were observed, which were also attenuated with wortmannin
and luzindole. These results strongly suggest that melatonin exerts its neuroprotective property in
astrocytes through the activation of plasma membrane receptors and then PI3K-Akt signaling pathway.

다국어 초록 (Multilingual Abstract)

Melatonin has been reported to protect neurons from a variety of neurotoxicity. However, the
underlying mechanism by which melatonin exerts its neuroprotective property has not yet been clearly
understood. We previously demonstrated that melatonin protected kainic acid-induced neuronal cell
death in mouse hippocampus, accompanied by sustained activation of Akt, a critical mediator of
neuronal survival. To further elucidate the neuroprotective action of melatonin, we examined in the
present study the causal mechanism how Akt signaling pathway is regulated by melatonin in a rat
primary astrocyte culture model. Melatonin resulted in increased astrocytic Akt phosphorylation, which
was significantly decreased with wortmannin, a specific inhibitor of PI3K, suggesting that activation
of Akt by melatonin is mediated through the PI3K-Akt signaling pathway. Furthermore, increased
Akt activation was also significantly decreased with luzindole, a non-selective melatonin receptor
antagonist. As downstream signaling pathway of Akt activation, increased levels of CREB
phoshorylation and GDNF expression were observed, which were also attenuated with wortmannin
and luzindole. These results strongly suggest that melatonin exerts its neuroprotective property in
astrocytes through the activation of plasma membrane receptors and then PI3K-Akt signaling pathway.

참고문헌 (Reference)

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