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Platelet mitochondrial respiratory chain function in Parkinson's disease
1Department of Neurology, University of Colorado Health Sciences Center, Denver 80262, USA.
Abstract:
Reports on mitochondrial respiratory chain (MRC) complex I (CI) dysfunction in the substantia nigra in Parkinson's disease (PD) support the oxidative stress hypothesis in the neuropathogenesis of PD. Studies in peripheral tissue have found variable decreased CI and occasionally other complex activity suggestive of systemic impairment of MRC function in PD; however, MRC activity may be influenced by numerous variables. We conducted spectrophotometric measurements of MRC function in platelet mitochondrial preparations in 13 individuals with PD and 9 age-matched controls (CON) and have identified additional variables that may affect MRC activity. Mean CI, CIII, CIV, and citrate synthase (CS) activities were similar between PD and CON. CIII and CIV, specific and CS-corrected, activities were significantly positively correlated with CI in combined and individual group data, with the exception of CIII CS-corrected and CIV specific activities in CON and PD, respectively. CIII and CS specific activities were negatively correlated with age in CON, but varied randomly in PD. In PD, CIII specific activity was 1.4-fold higher in those with a history of environmental risk factors for PD and CIV specific activity was lower in those with a positive family history of PD [8.34 +/- 0.74 (n = 4) vs. 12.4 +/- 1.1 (SEM) min-1 mg-1; p = 0.046]. Group heterogeneity, variables affecting enzyme activity, and intrinsic properties of cells may thus contribute to conflicting data in studies of MRC function in platelets and other tissues.
Insights
Parkinson's disease (PD) studies show mixed results on mitochondrial function. This research found no overall difference in mitochondrial respiratory chain complex activity between PD patients and controls, highlighting factors influencing variability.
Area of Science:
- Neuroscience
- Biochemistry
- Cell Biology
Background:
- Mitochondrial respiratory chain (MRC) complex I (CI) dysfunction is implicated in Parkinson's disease (PD) neuropathogenesis.
- Peripheral tissue studies show variable MRC function in PD, suggesting systemic impairment but influenced by many factors.
Purpose of the Study:
- To investigate MRC function in platelet mitochondria from PD patients and controls.
- To identify variables influencing MRC activity in PD.
Main Methods:
- Spectrophotometric measurement of MRC complex activities (CI, CIII, CIV) and citrate synthase (CS) in platelet mitochondrial preparations.
- Comparison between 13 PD individuals and 9 age-matched controls.
- Correlation analysis of enzyme activities with age and risk factors.
Main Results:
- No significant differences in mean CI, CIII, CIV, or CS activities between PD and control groups.
- Positive correlations between CIII/CIV and CI activities were observed, with exceptions.
- Age negatively correlated with CIII and CS activities in controls, but not in PD.
- In PD, CIII activity was higher with environmental risk factors; CIV activity was lower with a family history of PD.
Conclusions:
- Platelet mitochondrial MRC complex activities are similar between PD patients and controls.
- Group heterogeneity and influencing variables contribute to conflicting data in PD mitochondrial research.
- Further investigation is needed to understand the role of specific MRC complexes and influencing factors in PD pathogenesis.