Nitric oxide mediates membrane depolarization-promoted survival of rat neuronal PC12 cells.
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.
Kim
Tae Woon
TW
Department of Biochemistry, College of Medicine, Chung-Ang University, 221 Heuksuk-dong, Dongjak-ku, 156-756, Seoul, South Korea.
Lee
Chang-Han
CH
Choi
Chang-Young
CY
Kwon
Nyoun Soo
NS
Baek
Kwang Jin
KJ
Kim
Yang Gyun
YG
Yun
Hye-Young
HY
D000818:Animals; D002454:Cell Differentiation; D002462:Cell Membrane / Q000502:physiology; D002470:Cell Survival; D006152:Cyclic GMP / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D063065:Organophosphonates / Q000494:pharmacology; D016716:PC12 Cells; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D014162:Transfection; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
C436083:2-(2-oxo-2-((3,7,11-trimethyl-2,6,10-dodecatrienyl)oxy)aminoethyl)phosphonic acid, (2,2-dimethyl-1-oxopropoxy)methyl ester sodium; D020030:Nitric Oxide Donors; D063065:Organophosphonates; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins; D006152:Cyclic GMP; D011188:Potassium