TY - JOUR
T1 - Effect of dopaminergic neurotoxin MPTP/MPP+ on coenzyme Q content
AU - Dhanasekaran, Muralikrishnan
AU - Karuppagounder, Senthilkumar S.
AU - Uthayathas, Subramaniam
AU - Wold, Loren E.
AU - Parameshwaran, Kodeeswaran
AU - Jayachandra Babu, R.
AU - Suppiramaniam, Vishnu
AU - Brown-Borg, Holly
N1 - Funding Information:
This study was supported by Department of Pharmacal Sciences, Auburn University, Auburn, AL.
PY - 2008/7/18
Y1 - 2008/7/18
N2 - 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 μM) was incubated with SH-SY5Y human neuroblastoma cells and NG-108-15 (mouse/rat, neuroblastoma × glioma 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.
AB - 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 μM) was incubated with SH-SY5Y human neuroblastoma cells and NG-108-15 (mouse/rat, neuroblastoma × glioma 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.
KW - Coenzyme Q
KW - MPTP
KW - Oxidative stress
KW - Parkinson's disease
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U2 - 10.1016/j.lfs.2008.04.016
DO - 10.1016/j.lfs.2008.04.016
M3 - Article
C2 - 18565546
AN - SCOPUS:46749128091
VL - 83
SP - 92
EP - 95
JO - Life Sciences
JF - Life Sciences
SN - 0024-3205
IS - 3-4
ER -