The Role of Glycolysis and Gluconeogenesis in the Cytoprotection of Neuroblastoma Cells against 1-Methyl 4-Phenylpyridinium Ion Toxicity
Section snippets
INTRODUCTION
Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can lead to selective degeneration of dopaminergic neurons in the substantia nigra, resembling pathological features of Parkinson’s disease (PD) (Langston et al., 1983). 1-Methyl-4-phenylpyridinium (MPP+), the neurotoxic metabolite of MPTP, can reduce energy metabolism by impeding oxidative phosphorylation (OXPHOS) through inhibiting NADH dehydrogenase in Complex I of the electron transport chain (ETC) (Suzuki et al., 1990).
Materials
Mouse brain neuro-2A neuroblastoma cells (N2A) were obtained from American Type Culture Collection (Manassas, VA, USA). Dulbecco’s Modified Eagle Medium (DMEM), l-glutamine, fetal bovine serum—heat inactivated (FBS), Hank’s balanced salt solution (HBSS), phosphate buffered saline (PBS) and penicillin/streptomycin were supplied by Fischer Scientific, Mediatech (Pittsburgh, PA, USA). All other chemicals and supplies were purchased from Sigma Chemical (St. Louis, MO, USA).
Cell Culture Growth and Experimental Conditions
N2A cells were chosen for
RESULTS
A concentration–time curve for MPP+ toxicity was established and it was determined that 500 μM of MPP+ was adequate to achieve significant, but not total cell death at 24–36 h (data not shown). N2A cells were pretreated with experimental compounds for 2 h prior to treatment with MPP+ and samples were returned to the incubator for 24–36 h at 37 °C in 5% CO2/atmosphere. Each experimental batch was monitored with a timed control, to ensure a desired level of toxicity had been achieved. Moreover,
DISCUSSION
In the present study, we examined the propensity of alternative energy substrates to support anaerobic glycolysis and provide neuroprotection against MPP+. The data indicate that in addition to glucose, several monosaccharides and metabolic intermediates are capable of attenuating MPP+-induced toxicity. Monosaccharides are the smallest molecular form of carbohydrates and are the building blocks of all complex carbohydrates. The most common monosaccharides are glucose, fructose, galactose and
Acknowledgements
This work was supported by grants received from the National Institutes of Health (NCRR 03020 and GM 08111).
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