The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Melatonin Induces Akt Phosphorylation through Melatonin Receptor- and PI3K-Dependent Pathways in Primary Astrocytes

  • Kong, Pil-Jae (Department of Pharmacology, College of Medicine, Kangwon National University) ;
  • Byun, Jong-Seon (Department of Pharmacology, College of Medicine, Kangwon National University) ;
  • Lim, So-Young (Department of Anesthesiology, College of Medicine, Hallym University) ;
  • Lee, Jae-Jun (Department of Anesthesiology, College of Medicine, Hallym University) ;
  • Hong, Sung-Jun (Department of Pharmacology, College of Medicine, Kangwon National University) ;
  • Kwon, Kwang-Jun (Department of Oral and Maxillofacial Surgery, College of Dentistry, Kangnung National University) ;
  • Kim, Sung-Soo (Department of Pharmacology, College of Medicine, Kangwon National University)
  • Published : 2008.04.30
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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.

Keywords

References

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