Mitochondrial dysfunctions significantly contribute to the pathogenesis of Alzheimer's disease (AD). Here, we studied the relationship between AD and changes in the mitochondrial rates of respiration in blood platelets, respiratory chain complexes activity, and coenzyme Q10 plasma concentrations. In intact platelets obtained from AD patients, we observed a decrease in endogenous basal respiration rates, a decrease in the maximal capacity of the electron transport system (ETS), and higher respiratory rates after inhibiting complex I of the ETS. When normalized for citrate synthase activity, rotenone inhibited respiratory rates and complex I activity was significantly altered. In permeabilized platelets, mitochondrial respiration was completely rescued by the addition of complex I substrates. The changes in mitochondrial respiratory parameters were not associated with the progression of AD except for the capacity of the ETS in permeabilized platelets. In AD, complex I activity was increased, complex IV activity was decreased, and coenzyme Q10 plasma concentrations were decreased. Our data indicate that both insufficiency in substrates entering into the oxidative phosphorylation system and functional disturbances in the ETS complex are responsible for the decrease in respiration observed in intact platelets in AD patients. Analyses of complex IV activity, the respiratory rates of intact platelets, and the capacity of the ETS in permeabilized platelets may enable the characterization of mitochondrial dysfunctions in the initial stage of AD.
- MeSH
- Alzheimerova nemoc genetika metabolismus MeSH
- apolipoproteiny E genetika MeSH
- biologické markery metabolismus MeSH
- citrátsynthasa metabolismus MeSH
- frekvence genu MeSH
- lidé středního věku MeSH
- lidé MeSH
- mitochondrie metabolismus MeSH
- polymorfismus genetický MeSH
- respirační komplex I metabolismus MeSH
- respirační komplex IV metabolismus MeSH
- ROC křivka MeSH
- senioři MeSH
- trombocyty metabolismus MeSH
- ubichinon analogy a deriváty krev MeSH
- záznam o duševním stavu MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVE: Information concerning un-supplemented plasma concentrations of ubiquinol-10 in coronary artery disease patients is still controversial. The aim of this study is to determine the levels of plasma ubiquinol-10 and ratios of ubiquinol-10 to plasma lipids in consecutive patients with different angiographic findings. SUBJECTS AND METHODS: Thirty-six consecutive patients who underwent coronary angiography were split in two groups with different atherosclerotic changes. These patients were un-supplemented with antioxidants and were not treated by lipid-lowering medication. We have measured a plasma level of ubiquinol-10 using high-performance liquid chromatography with coulometric detection. Conventional plasma lipids, markers of oxidative stress and other widely accepted risk factors of atherosclerosis have been determined too. RESULTS: Plasma ubiquinol-10 to low-density lipoprotein cholesterol (LDL-C) ratios in patients with different angiographic findings have been found as 180+/-69 and 132+/-43, respectively (p=0.020). The ubiquinol-10/LDL-C ratio was significantly lower in angiographically positive patients. There were also significant differences in ubiquinol-10 per total cholesterol (109+/-47 and 80+/-26, respectively; p=0.031), per triglycerides (426+/-191 and 237+/-86, respectively; p=0.002) and per the sum of triglycerides and total cholesterol (86+/-35 and 61+/-20, respectively; p=0.013). CONCLUSIONS: There have not been found any significant differences between levels of widely accepted risk factors for genesis and progress of atherosclerotic changes in these two groups of patients. Only the level of triglycerides and the total cholesterol minus high-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio were significantly higher in patients with stenosis. This ratio correlated with the ubiquinol-10/LDL-C ratio, which was significantly lower in patients with stenosis. Our results indicate that the ratio of ubiquinol-10/LDL-C is likely to be a risk factor for atherogenesis.
- MeSH
- antioxidancia farmakologie MeSH
- biologické markery krev MeSH
- dospělí MeSH
- financování organizované MeSH
- koronární angiografie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipidy analýza MeSH
- nemoci koronárních tepen diagnóza metabolismus MeSH
- rizikové faktory MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ubichinon analogy a deriváty krev MeSH
- vitamin E metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- MeSH
- antioxidancia analýza MeSH
- bronchiální astma krev MeSH
- lidé MeSH
- ubichinon analogy a deriváty krev MeSH
- Check Tag
- lidé MeSH
- MeSH
- antioxidancia krev MeSH
- beta-karoten krev MeSH
- dospělí MeSH
- finanční podpora výzkumu jako téma MeSH
- lidé středního věku MeSH
- lidé MeSH
- malondialdehyd krev MeSH
- nemoci ledvin diagnóza komplikace terapie MeSH
- peroxidace lipidů MeSH
- senioři MeSH
- ubichinon krev MeSH
- vitamin E krev MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- přehledy MeSH
- srovnávací studie MeSH
- Geografické názvy
- Slovenská republika MeSH
