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Complex-1 activity and 18F-DOPA uptake in genetically engineered mouse model of Parkinson's disease and the neuroprotective role of coenzyme Q10.
Brain Res Bull. 2006 Jun 15; 70(1):22-32.BR

Abstract

Regional distribution of coenzyme Q10 and mitochondrial complex-1 activity were estimated in the brains of control-(C57BL/6), metallothionein knock out-, metallothionein transgenic-, and homozygous weaver mutant mice; and human dopaminergic (SK-N-SH) cells with a primary objective to determine the neuroprotective potential of coenzyme Q10 in Parkinson's disease. Complex-1 activity as well as coenzyme Q10 were significantly higher in the cerebral cortex as compared to the striatum in all the genotypes examined. Complex-1 activity and coenzyme Q10 were significantly reduced in weaver mutant mice and metallothionein knock out mice, but were significantly increased in metallothionein transgenic mice. The reduced complex-1 activity and 18F-DOPA uptake occurred concomitantly with negligible differences in the coenzyme Q10 between in the cerebral cortex and striatum of weaver mutant mice. Administration of coenzyme Q10 increased complex-1 activity and partially improved motoric performance in weaver mutant mice. Direct exposure of rotenone also reduced coenzyme Q10, complex-1 activity, and mitochondrial membrane potential in SK-N-SH cells. Rotenone-induced down-regulation of complex-1 activity was attenuated by coenzyme Q10 treatment, suggesting that complex-1 may be down regulated due to depletion of coenzyme Q10 in the brain. Therefore, metallothionein-induced coenzyme Q10 synthesis may provide neuroprotection by augmenting mitochondrial complex-1 activity in Parkinson's disease.

Authors+Show Affiliations

Department of Pharmacology, University of North Dakota School of Medicine and Health Sciences, 501 North Columbia Road, Grand Forks, ND 58203, United States.No affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16750479

Citation

Sharma, Sushil K., et al. "Complex-1 Activity and 18F-DOPA Uptake in Genetically Engineered Mouse Model of Parkinson's Disease and the Neuroprotective Role of Coenzyme Q10." Brain Research Bulletin, vol. 70, no. 1, 2006, pp. 22-32.
Sharma SK, El Refaey H, Ebadi M. Complex-1 activity and 18F-DOPA uptake in genetically engineered mouse model of Parkinson's disease and the neuroprotective role of coenzyme Q10. Brain Res Bull. 2006;70(1):22-32.
Sharma, S. K., El Refaey, H., & Ebadi, M. (2006). Complex-1 activity and 18F-DOPA uptake in genetically engineered mouse model of Parkinson's disease and the neuroprotective role of coenzyme Q10. Brain Research Bulletin, 70(1), 22-32.
Sharma SK, El Refaey H, Ebadi M. Complex-1 Activity and 18F-DOPA Uptake in Genetically Engineered Mouse Model of Parkinson's Disease and the Neuroprotective Role of Coenzyme Q10. Brain Res Bull. 2006 Jun 15;70(1):22-32. PubMed PMID: 16750479.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Complex-1 activity and 18F-DOPA uptake in genetically engineered mouse model of Parkinson's disease and the neuroprotective role of coenzyme Q10. AU - Sharma,Sushil K, AU - El Refaey,Hesham, AU - Ebadi,Manuchair, Y1 - 2005/12/27/ PY - 2005/10/26/received PY - 2005/11/13/accepted PY - 2006/6/6/pubmed PY - 2006/9/6/medline PY - 2006/6/6/entrez SP - 22 EP - 32 JF - Brain research bulletin JO - Brain Res Bull VL - 70 IS - 1 N2 - Regional distribution of coenzyme Q10 and mitochondrial complex-1 activity were estimated in the brains of control-(C57BL/6), metallothionein knock out-, metallothionein transgenic-, and homozygous weaver mutant mice; and human dopaminergic (SK-N-SH) cells with a primary objective to determine the neuroprotective potential of coenzyme Q10 in Parkinson's disease. Complex-1 activity as well as coenzyme Q10 were significantly higher in the cerebral cortex as compared to the striatum in all the genotypes examined. Complex-1 activity and coenzyme Q10 were significantly reduced in weaver mutant mice and metallothionein knock out mice, but were significantly increased in metallothionein transgenic mice. The reduced complex-1 activity and 18F-DOPA uptake occurred concomitantly with negligible differences in the coenzyme Q10 between in the cerebral cortex and striatum of weaver mutant mice. Administration of coenzyme Q10 increased complex-1 activity and partially improved motoric performance in weaver mutant mice. Direct exposure of rotenone also reduced coenzyme Q10, complex-1 activity, and mitochondrial membrane potential in SK-N-SH cells. Rotenone-induced down-regulation of complex-1 activity was attenuated by coenzyme Q10 treatment, suggesting that complex-1 may be down regulated due to depletion of coenzyme Q10 in the brain. Therefore, metallothionein-induced coenzyme Q10 synthesis may provide neuroprotection by augmenting mitochondrial complex-1 activity in Parkinson's disease. SN - 0361-9230 UR - https://www.unboundmedicine.com/medline/citation/16750479/Complex_1_activity_and_18F_DOPA_uptake_in_genetically_engineered_mouse_model_of_Parkinson's_disease_and_the_neuroprotective_role_of_coenzyme_Q10_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0361-9230(05)00462-4 DB - PRIME DP - Unbound Medicine ER -