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Anaerobic glycolysis and ATP production after complex I inhibition by MPP+ in C‐6 glioma cells
Author(s) -
Williams Zakia R,
Veira Maxwell,
Soliman Karam F
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1133-b
Subject(s) - anaerobic glycolysis , glycolysis , glioma , anaerobic exercise , chemistry , production (economics) , biochemistry , microbiology and biotechnology , cancer research , metabolism , biology , physiology , economics , macroeconomics
The neurotoxin 1‐methy‐4‐phenylpyridinium (MPP+) is commonly used to induce Parkinsonism through its ability to inhibit mitochondrial complex I. The objective of this experiment was to demonstrate that inhibition of mitochondrial complex I (NADH: Ubiquione Oxioreductase) via MPP+ would interfere with oxidative phosphorylation and that glucose supplementation will augment cell survival and ATP production using the cytoplasmic anaerobic pathway. In this study, C6 glioma cells were treated with 10mM glucose followed by various concentrations of MPP+, 500 uM, 1 mM, and 2mM. Twenty‐four hours post treatment, control and treatment groups were analyzed for cell viability complex I activity, ATP production and mitochondrial transmembrane potential (MTP). The results indicated that cell viability of MPP+ and MPP+ co‐treated with glucose was significantly different. Analysis of complex I activity revealed a significant decrease in all MPP+ treated cells. Furthermore, glucose supplementation did not augment complex I activity in concomitant treated glucose and MPP+ groups. The co‐treated groups produced significantly higher ATP than MPP+ alone. MTP measurements using Rhodamine 123 in cells treated with MPP+ and glucose revealed drastic reduction in MTP. The data also indicated that glucose addition did not restore MTP of cells exposed to MPP+. It was concluded from this study that glucose supplementation can sustain cellular viability post mitochondria complex I inhibition through the anaerobic production of ATP. (Supported by NIH Grant RR03020)