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The Protective Role of d-Glucose Against 1-Methyl-4-Phenylpyridinium Ion (MPP+): Induced Mitochondrial Dysfunction in C6 Astroglial Cells

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Abstract

Impaired mitochondrial function in glial and neuronal cells in the substantia nigra is one of the most likely causes of Parkinson’s disease. In this study, we investigated the protective role of glucose on early key events associated with MPP+-induced changes in rat C6 astroglial cells. Studies were carried out to examine alterations in mitochondrial respiratory status, membrane potential, glutathione levels, and cell cycle phase inhibition at 48 h in 2 and 10 mM glucose in media. The results obtained suggest that MPP+ caused significant cell death in 2 mM glucose with LC50 0.14 ± 0.005 mM, while 10 mM glucose showed highly significant protection against MPP+ toxicity with LC50 0.835 ± 0.03 mM. This protection was not observed with cocaine, demonstrating its compound specificity. MPP+ in 2 mM glucose decreased significantly mitochondrial respiration, membrane potential and glutathione levels in a dose dependent manner, while 10 mM glucose significantly restored them. MPP+ in 2 mM glucose arrested the cells at G0/G1 and G2/M phases, demonstrating its dual inhibitory effects. However, in 10 mM glucose, MPP+ caused G0/G1 arrest only. In summary, the results suggest that loss of cell viability in 2 mM glucose group with MPP+ treatments was due to mitochondrial dysfunction caused by multilevel mechanism, involving significant decrease in mitochondrial respiration, membrane potential, glutathione levels, and dual arrest of cell phases, while 10 mM glucose rescued astroglial cells from MPP+ toxicity by significant maintenance of these factors.

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Acknowledgments

The authors acknowledge the critical reading of the manuscript and the valuable suggestions of Dr. Sandra Suther. This study was supported by a grant obtained from the National Institutes of Health, Division of Research Resources, Research Centers in Minority Institution (RCMI) G12 RR 03020.

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Correspondence to Karam F. A. Soliman.

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Badisa, R.B., Darling-Reed, S.F. & Soliman, K.F.A. The Protective Role of d-Glucose Against 1-Methyl-4-Phenylpyridinium Ion (MPP+): Induced Mitochondrial Dysfunction in C6 Astroglial Cells. Neurochem Res 35, 1413–1421 (2010). https://doi.org/10.1007/s11064-010-0200-9

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