title: Sodium nitroprusside, a nitric oxide donor, fails to bypass the block of neuronal differentiation in PC12 cells imposed by a dominant negative Ras protein.
abstract: Nitric oxide (NO) is a mediator of a diverse array of inter- and intracellular signal transduction processes. The aim of the present study was to analyze its possible role as a second messenger in the process of neuronal differentiation of PC12 pheochromocytoma cells. Upon NGF treatment wildtype PC12 cells stop dividing and develop neurites. In contrast, a PC12 subclone (designated M-M17-26) expressing a dominant-negative mutant Ras protein keeps proliferating and fails to grow neurites after NGF treatment. Sodium nitroprusside (SNP), an NO donor, was found to induce the p53 protein and to inhibit proliferation of both PC12 and M-M17-26 cells, but failed to induce neuronal differentiation in these cell lines. Key signaling pathways (the ERK and Akt pathways) were also not affected by SNP treatment, and the phosphorylation of CREB transcription factor was only slightly stimulated. It is thus concluded from the results presented in this paper that NO is unable to activate signaling proteins acting downstream or independent of Ras that are required for neuronal differentiation.
authors.affiliation: Department of Medical Biology, Medical School, University of Pécs, 7624, Pécs, Szigeti u. 12, Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Bátor
authors.forename: Judit
authors.initials: J
authors.lastname: Varga
authors.forename: Gergely
authors.initials: G
authors.lastname: Berta
authors.forename: Tamar
authors.initials: T
authors.lastname: Barbakadze
authors.forename: David
authors.initials: D
authors.lastname: Mikeladze
authors.forename: Jeremy
authors.initials: J
authors.lastname: Ramsden
authors.forename: József
authors.initials: J
authors.lastname: Szeberényi
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020932:Nerve Growth Factor / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000378:metabolism / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D016716:PC12 Cells; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D020030:Nitric Oxide Donors; D016159:Tumor Suppressor Protein p53; D009599:Nitroprusside; D009569:Nitric Oxide; D020932:Nerve Growth Factor; D051057:Proto-Oncogene Proteins c-akt; D018631:ras Proteins