Effect of dopaminergic neurotoxin MPTP/MPP+ on coenzyme Q content.
Coenzyme Q10, an endogenous lipophilic antioxidant, plays an indispensable role in ATP synthesis. The therapeutic value of coenzyme Q10 in Parkinson's disease and other neurodegenerative disorders is still being tested and the preliminary results are promising. The 1-methyl-4-phenyl-1, 2, 3, 6 tetrahydropyridine (MPTP)-treated mouse is a valid and accepted animal model for Parkinson's disease. 1-methyl-4-phenylpyridinium (MPP(+)) is an active toxic metabolite of MPTP. MPP(+) and MPTP are known to induce oxidative stress and mitochondrial dysfunction. However, the effect of MPP(+) and MPTP on coenzyme Q is not clearly understood. The present study investigated the in vitro and in vivo effect of MPP(+) and MPTP on coenzyme Q content. Coenzyme Q content was measured using HPLC-UV detection methods. In the in vitro studies, MPP(+) (0-50 microM) was incubated with SH-SY5Y human neuroblastoma cells and NG-108-15 (mouse/rat, neuroblastomaxglioma hybrid) cells. MPP(+) concentration dependently increased coenzyme Q10 content in SH-SY5Y cells. In NG-108-15 cells, MPP(+) concentration dependently increased both coenzyme Q9 and Q10 content. In the in vivo study, mice were administered with MPTP (30 mg/kg, twice 16 h apart) and sacrificed one week after the last administration. Administration of MPTP to mice significantly increased coenzyme Q9 and coenzyme Q10 levels in the nigrostriatal tract. However, MPTP did not affect the coenzyme Q content in the cerebellum, cortex and pons. This study demonstrated that MPP(+)/MPTP significantly affected the coenzyme Q content in the SH-SY5Y and NG-108 cells and in the mouse nigrostriatal tract.
Dhanasekaran
Muralikrishnan
M
Division of Pharmacology and Toxicology, Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA. dhanamu@auburn.edu
Karuppagounder
Senthilkumar S
SS
Uthayathas
Subramaniam
S
Wold
Loren E
LE
Parameshwaran
Kodeeswaran
K
Jayachandra Babu
R
R
Suppiramaniam
Vishnu
V
Brown-Borg
Holly
H
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000818:Animals; D045744:Cell Line, Tumor; D002531:Cerebellum / Q000187:drug effects / Q000201:enzymology; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology; D002851:Chromatography, High Pressure Liquid; D015259:Dopamine Agents / Q000633:toxicity*; D006801:Humans; D020267:MPTP Poisoning / Q000201:enzymology / Q000209:etiology; D051379:Mice; D008810:Mice, Inbred C57BL; D011149:Pons / Q000187:drug effects / Q000201:enzymology; D014451:Ubiquinone / Q000032:analysis / Q000378:metabolism*
D015259:Dopamine Agents; D014451:Ubiquinone; D015655:1-Methyl-4-phenylpyridinium