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KMID : 0578320100300050427
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Molecules and Cells
2010 Volume.30 No. 5 p.427 ~ p.433
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Protective Effect of Urocortin on 1-Methyl-4-Phenylpyridinium-Induced Dopaminergic Neuronal Death
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Kim Yon-Jung
Park Myoung-Kyu
Chung Sung-Kwon
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Abstract
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Recent studies have indicated that the corticotropin relea-sing hormone (CRF)-related peptide, urocortin, restores key indicators of damage in animal models for Parkinson's disease (PD). However, the molecular mechanism for the neuroprotective effect of urocortin is unknown. 1-Methy-4-phenylpyridinium (MPP+) induces dopaminergic neuronal death. In the present study, MPP+-induced neuroblastoma SH-SY5Y cell death was significantly attenuated by urocortin in a concentration-dependent manner. The protective effect of urocortin involved the activation of CRF receptor type 1, resulting in the increase of cyclic AMP (cAMP) levels. Various cAMP-enhancing reagents mimicked the effect of urocortin, while inhibitors for protein kinase A (PKA) blocked the effect of urocortin, strongly implicating the involvement of cAMP-PKA pathway in the neuroprotec-tive effect of urocortin on MPP+-induced cell death. As the downstream of this signal pathway, urocortin promoted phosphorylation of both glycogen synthase kinase 3β and extracellular signal-regulated kinases, which are known to promote cell survival. These neuroprotective signaling pathways of urocortin may serve as potential therapeutic targets for PD.
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KEYWORD
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1-methy-4-phenylpyridinium, cAMP, dopamine neuron, protein Kinase A, urocortin
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