Abstract Details

Title NADPH Treatment Decreases C6 Glioma Cell Survival by Increasing oxidative stress

Topic Neuro-oncology

Presentation(s) S35 - (-)

Poster/Presentation
Number 002

Objective

Background NADPH (nicotinamide adenine dinucleotide phosphate, reduced form) plays pivotal roles in antioxidation and reductive biosynthesis. However, the effect of NADPH treatment on cell survival is unknown. In this study, we determined the effect of NADPH treatment on the survival of glioma cells.

Design/Methods Lactate dehydrogenase (LDH) assay;Determinations of nuclear condensation;Flow cytometry-based PI staining;Trypan blue Assay;Dihydroethidium (DHE) assay;Data were assessed by one-way ANOVA, followed by Student-Newman-Keuls post hoc test.

Results Treatment of C6 glioma cells with as low as 1 [mu]M NADPH for 24 hrs induced a significant decrease in the survival of the glioma cells, while NADPH treatment had no effect on the survival of primary astrocyte cultures. We also found that NADPH treatment increased intracellular oxidative stress. Three antioxidants and the NADPH oxidase inhibitor, apocynin, attenuated the effect of NADPH. Poly(ADP-ribose)polymerase (PARP) activation appears to be a downstream effector of the oxidative stress, since PARP inhibitors reduced the effect of NADPH. Calcium chelator, BAPTAAM,also attenuated the effect of NADPH.

Conclusions Collectively,these data indicate a novel property of NADPH: NADPH decreases glioma cell survival by inducing the NADPH oxidase-dependent increase in oxidative stress and by PARP activation. These results also suggest a potential therapeutic effect of NADPH on gliomas.

Authors/Disclosures
PRESENTER	No disclosure on file
	No disclosure on file
Maria A. Rocca (Neuroimaging Research Unit)	Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen, Bristol Myers Squibb, Eli Lilly, Janssen, Roche. Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for AstraZaneca, Biogen, Bristol Myers Squibb, Bromatech, Celgene, Genzyme, Horizon Therapeutics Italy, Merck Serono SpA, Novartis, Roche, Sanofi and Teva. The institution of Maria Assunta Rocca has received research support from MS Society of Canada, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla.
	No disclosure on file
	No disclosure on file

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