Decreased expression of the NADH:ubiquinone oxidoreductase (complex I) subunit 4 in 1-methyl-4-phenylpyridinium-treated human neuroblastoma SH-SY5Y cells

Oxidative stress and mitochondrial dysfunction have been implicated in Parkinson's disease (PD) pathology. NADH:ubiquinone oxidoreductase (complex I) (EC 1.6.99.3) enzyme activity is aberrant in both PD and 1-methyl-4-phenylpyridinium (MPP+) models of PD. Reverse transcription polymerase chain reaction of RNA isolated from MPP+-treated human neuroblastoma SH-SY5Y cells identified changes in steady-state mRNA levels of the mitochondrial transcript for subunit 4 of complex I (ND4). Expression of ND4 decreased to nearly 50% after 72 h of MPP+ (1 mM) exposure. The expression of other mitochondrial transcripts did not change significantly under the same conditions. Pre-incubation of cells with the free-radical spin-trap, N-tert-butyl-alpha-(2-sulfophenyl)-nitrone prior to MPP+ exposure, prevented decreases in cell viability and ND4 expression. This suggests that functional defects in complex 1 enzyme activity in PD and MPP+ toxicity may result from changes in steady-state mRNA levels and that free radicals may be important in this process. (C) 2001 Published by Elsevier Science Ireland Ltd.