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Anaerobic Glycolysis Protection against 1-Methy-4-Phenylpyridinium (MPP+) Toxicity in C6 Glioma Cells

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Abstract

The neurotoxin 1-methy-4-phenylpyridinium (MPP+) is used for its’ capacity to induce Parkinsonism through its inhibitory effects on mitochondrial complex I. This inhibition disrupts cellular energy formation and aerobic glycolysis. The objective of this study was to demonstrate that the toxic effect of mitochondrial aerobic pathway inhibition with MPP+ can be reduced by stimulating anaerobic glycolysis using glucose supplementation. In this study, C6 Glioma cell viability was examined in the presence of different concentrations of MPP alone and with the addition of glucose. The results obtained indicate that there was a significant increase (P < 0.001) in cell viability in cells treated with glucose and MPP+ verses cells treated with MPP+ alone. Fluorometric analysis using 100 uM Rhodamine 123 indicated mitochondrial membrane potential was not restored in MPP+ treated cells with glucose; however, normal cell viability was confirmed using 2 ug/ml Fluorescein diacetate. This dual fluorescence indicated mitochondrial damage from MPP+ while glucose augmented cell survival. Further confirmation of cell survival upon damage to the mitochondria was evident in TUNEL staining. Positive staining was prominent only in MPP+ treatment groups alone, while control and co-treated groups exhibited little to no TUNEL staining. ATP measurements of all MPP+ treated groups exhibited a significant (P < 0.001) decrease verses control. Groups co-treated with MPP+ and glucose revealed a significant increase (250 μM group: P < 0.001) in ATP. It was concluded from this study that glucose supplementation was able to sustain cellular viability and ATP production through anaerobic glycolysis despite the inhibitory effect of MPP+ on aerobic glycolysis.

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Acknowledgments

This work was supported by a grant received from the National Institutes of Health (RR 03020).

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  1. College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL, 32307, USA

    Zakia R. Williams, Carl B. Goodman & Karam F. A. Soliman

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  1. Zakia R. Williams
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Correspondence to Karam F. A. Soliman.

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Williams, Z.R., Goodman, C.B. & Soliman, K.F.A. Anaerobic Glycolysis Protection against 1-Methy-4-Phenylpyridinium (MPP+) Toxicity in C6 Glioma Cells. Neurochem Res 32, 1071–1080 (2007). https://doi.org/10.1007/s11064-006-9276-7

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