Melatonin Induces Akt Phosphorylation through Melatonin Receptor- and PI3K-Dependent Pathways in Primary Astrocytes.
10.4196/kjpp.2008.12.2.37
- Author:
Pil Jae KONG
1
;
Jong Seon BYUN
;
So Young LIM
;
Jae Jun LEE
;
Sung Jun HONG
;
Kwang Jun KWON
;
Sung Soo KIM
Author Information
1. Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon 200-701, Korea. ksslsy@kangwon.ac.kr
- Publication Type:Original Article
- Keywords:
Melatonin;
Akt phosphorylation;
Melatonin receptor;
luzindole;
PI3K;
Primary astrotyctes
- MeSH:
Androstadienes;
Animals;
Astrocytes;
Cell Death;
Cell Membrane;
Glial Cell Line-Derived Neurotrophic Factor;
Hippocampus;
Melatonin;
Mice;
Neurons;
Phosphorylation;
Rats;
Receptors, Melatonin;
Tryptamines
- From:The Korean Journal of Physiology and Pharmacology
2008;12(2):37-41
- CountryRepublic of Korea
- Language:English
-
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.
