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

• Published in: Neuroscience letters 2001-06, Vol.306 (3), p.145-148
• Main Authors: Conn, Kelly J, Ullman, M.David, Eisenhauer, Patricia B, Fine, Richard E, Wells, John M
• Format: Article
• Language: English
• Subjects: 1-Methyl-4-phenyl-pyridinium; 1-Methyl-4-phenylpyridinium - toxicity; Biological and medical sciences; Complex I; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Electron Transport Complex I; Gene Expression Regulation, Enzymologic - drug effects; Herbicides - toxicity; Humans; Medical sciences; Mitochondria - enzymology; MPP; N-tert-butyl-α-(2-sulfophenyl)-nitrone; NADH, NADPH Oxidoreductases - genetics; NADH:Ubiquinone Oxidoreductase subunit 4; Neuroblastoma; Neurology; Neurons - drug effects; Neurons - physiology; Parkinson Disease - metabolism; Parkinson's disease; Reverse transcription-polymerase chain reaction; RNA, Messenger - analysis; Tumor Cells, Cultured
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/S0304-3940(01)01888-2

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-α-(2-sulfophenyl)-nitrone prior to MPP + exposure, prevented decreases in cell viability and ND4 expression. This suggests that functional defects in complex I 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.