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Protocol for Culturing Sympathetic Neurons from Rat Superior Cervical Ganglia (SCG)
Published on: January 30, 2009
Nitric oxide mediates membrane depolarization-promoted survival of rat neuronal PC12 cells
Tae Woon Kim1, Chang-Han Lee, Chang-Young Choi
1Department of Biochemistry, College of Medicine, Chung-Ang University, 221 Heuksuk-dong, Dongjak-ku, 156-756, Seoul, South Korea.
Abstract:
Membrane depolarization promotes neuronal survival through increases in intracellular calcium. Nitric oxide (NO) is a signaling molecule involved in many neuronal activity-dependent events. Since neuronal NO is generated by NO synthase (NOS) in a calcium-dependent manner and was shown to promote cell survival, we tested whether NO is involved in depolarization-promoted survival in neuronally differentiated PC12 cells. NOS inhibitor attenuated depolarization-promoted survival and NO donors promoted survival. This effect was partially cGMP-dependent as a guanylyl cyclase inhibitor decreased NO-promoted survival. Ras inhibitor, Erk blocker or phosphatidylinositol 3-kinase inhibitor decreased depolarization- or NO donor-promoted survival. Depolarization-induced Ras activation was blocked by NOS inhibitor. Inducible expression of dominant negative Ras or S-nitrosylation-defective Ras attenuated depolarization- or NO donor-promoted survival. Thus, NO might be a mediator via Ras and cGMP pathways in depolarization-promoted survival in neuronal PC12 cells.
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