A role of nitric oxide in neurite outgrowth of neuroblastoma cells triggered by mevastatin or serum reduction.
Neuroblastoma cell lines are commonly used as a model to study neuronal differentiation as they retain the capacity to differentiate into a neuronal-like phenotype. It is of great medical interest to understand the signalling pathways biasing differentiation versus proliferation. Neuroblastoma cells differentiate in response to serum reduction or addition of the cholesterol synthesis inhibitor mevastatin. The responsible pathways are not well characterized. In Neuro2a neuroblastoma cells, we found that mevastatin and serum withdrawal triggered the production of nitric oxide (NO). In addition, the differentiation of Neuro2a cells and the activation of Akt/PKB triggered by serum withdrawal could be blocked by addition of the NO synthetase (NOS) inhibitor l-NAME. Moreover, mevastatin and serum withdrawal rapidly increased the expression of the neuronal NOS isoform nNOS. However, addition of an NO donor SNP per se did not trigger neurite outgrowth. Taken together, we report for the first time a role of NO in neurite outgrowth of neuroblastoma cells triggered by mevastatin or serum reduction.
Department of Neurology, Eginitio Hospital, University of Athens, Vas. Sophias 74, Athens 11528, Greece.
Maria Elephteria
ME
Evangelopoulos
Stefan
S
Wüller
Joachim
J
Weis
Alexander
A
Krüttgen
D000818:Animals; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D016895:Culture Media, Serum-Free; D004789:Enzyme Activation; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D009599:Nitroprusside / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
D016895:Culture Media, Serum-Free; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D020030:Nitric Oxide Donors; D009599:Nitroprusside; C012258:mevastatin; D009569:Nitric Oxide; D008148:Lovastatin; D052248:Nitric Oxide Synthase Type I; D051057:Proto-Oncogene Proteins c-akt; D019331:NG-Nitroarginine Methyl Ester