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Cisplatin-induced apoptotic cell death in mouse hybrid neurons is blocked by antioxidants through suppression of cisplatin-mediated accumulation of p53 but not of Fas/Fas ligand.

Authors
Park, SA; Choi, KS; Bang, JH; Huh, K; Kim, SU
Citation
Journal of neurochemistry, 75(3):946-953, 2000
Journal Title
Journal of neurochemistry
ISSN
0022-30421471-4159
Abstract
Peripheral neuropathy following cisplatin treatment is a major limiting factor in cisplatin chemotherapy of cancer patients. We investigated the pathomechanism underlying cisplatin neuropathy using a mouse dorsal root ganglion neuron-neuroblastoma hybrid cell line (N18D3) developed in our laboratory. DNA fragmentation, a characteristic feature of apoptosis, was induced in hybrid neurons following treatment with cisplatin. Accumulation of p53, Fas, and Fas ligand (Fas-L) was also demonstrated in these neurons. Preincubation with N-acetylcysteine (NAC), a precursor of glutathione, blocked cisplatin-induced apoptosis completely, whereas Trolox, a vitamin E analogue, blocked it partially. Cisplatin-induced p53 accumulation was suppressed by NAC treatment, whereas p53 accumulation was retarded by Trolox treatment. In contrast, neither NAC nor Trolox showed any inhibitory effect on cisplatin-induced Fas/Fas-L accumulation. These results suggest that the neuroprotective effects of antioxidants against cisplatin-induced neurotoxicity in hybrid neurons are mediated mainly through the inhibition of p53 accumulation but not of Fas/Fas-L accumulation by these antioxidants.
MeSH terms
Acetylcysteine/pharmacologyAnimalsAntigens, CD95/*metabolismAntioxidants/*pharmacologyApoptosis/*drug effectsCell Nucleus/drug effectsCell Survival/drug effectsChromans/pharmacologyCisplatin/antagonists & inhibitors/*toxicityDNA FragmentationFas Ligand ProteinGanglia, SpinalHybrid Cells/cytology/*drug effects/physiologyKineticsMembrane Glycoproteins/metabolismMiceNeuroblastomaNeurons, Afferent/cytology/*drug effects/physiologyTumor Suppressor Protein p53/*metabolism
PMID
10936175
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
Journal Papers > School of Medicine / Graduate School of Medicine > Neurology
AJOU Authors
최, 경숙허, 균김, 승업
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