Increased resistance to nitric oxide cytotoxicity associated with differentiation of neuroblastoma-glioma hybrid (NG108-15) cells.
Nitric oxide (NO), synthesized by the enzyme nitric oxide synthase (NOS), acts as an intercellular messenger associated with various physiological and pathological events. In this study, we investigated whether there exits a difference in the vulnerability to NO-induced cytotoxicity between undifferentiated and differentiated NG108-15 cells, and if so, the mechanisms responsible for the difference. Following a 7- to 8-day exposure to dibutyryl cAMP (dbcAMP), NG108-15 cells exhibited a neuron-like morphology associated with the expression of the neuronal protein, synaptophysin, and with increased NADPH-d activity. Neuron-like differentiated NG108-15 cells acquired resistance to exogenously applied NO. This increased resistance to NO toxicity in differentiated cells was almost completely cancelled out by inhibiting the activity of superoxide dismutase (SOD), but not by inhibiting the activity of NOS. The present study suggested that the activity of SOD increased in parallel with the activity of NOS associated with differentiation and was crucial for the acquired resistance to NO toxicity in differentiated cells.
Kawahara
Koichi
K
Laboratoire of Biomedical Control, Research Institute for Electronic Science, Hokkaido University, Sapporo, Japan. kawahara@bmc.es.hokudai.ac.jp
Saitoh
Munetaka
M
Nakajima
Takayuki
T
Sato
Hideomi
H
Tanaka
Motoki
M
Tojima
Takuro
T
Ito
Eturo
E
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002454:Cell Differentiation; D008058:Dihydrolipoamide Dehydrogenase / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D006822:Hybrid Cells / Q000187:drug effects; D007124:Immunoenzyme Techniques; D051379:Mice; D009249:NADP / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000473:pathology; D009569:Nitric Oxide / Q000633:toxicity*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D011817:Rabbits; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D016708:Synaptophysin; D009569:Nitric Oxide; D009249:NADP; D003994:Bucladesine; C496320:NOS1 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; D013482:Superoxide Dismutase; D008058:Dihydrolipoamide Dehydrogenase