The protective role of D-glucose against 1-methyl-4-phenylpyridinium ion (MPP+): induced mitochondrial dysfunction in C6 astroglial cells.
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 LC(50) 0.14 +/- 0.005 mM, while 10 mM glucose showed highly significant protection against MPP(+) toxicity with LC(50) 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.
College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA.
Ramesh B
RB
Badisa
Selina F
SF
Darling-Reed
Karam F A
KF
Soliman
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation; D019069:Cell Respiration / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006540:Herbicides / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D051381:Rats
D006540:Herbicides; D005978:Glutathione; D005947:Glucose; D015655:1-Methyl-4-phenylpyridinium