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 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.
Conn
K J
KJ
Department of Veterans Affairs, VA Medical Center, 200 Springs Road, Bedford, MA 01730, USA. conn.kelly_j@bedford.va.gov
Ullman
M D
MD
Eisenhauer
P B
PB
Fine
R E
RE
Wells
J M
JM
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D042967:Electron Transport Complex I; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006540:Herbicides / Q000633:toxicity*; D006801:Humans; D008928:Mitochondria / Q000201:enzymology; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics*; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010300:Parkinson Disease / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured
D006540:Herbicides; D012333:RNA, Messenger; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I; D015655:1-Methyl-4-phenylpyridinium