摘要
线粒体功能障碍明显地促成了阿兹海默氏症(AD)的病理进程。在这里,我们研究了AD与血小板线粒体呼吸频率、呼吸链复合物活性和辅酶Q10血浆浓度的变化之间的关系。从AD患者获取完整的血小板,我们观察到内源性基础呼吸频率降低,电子传递系统(ETS)的最大容量减少,抑制ETS的复和物I后呼吸频率增高。当柠檬酸合酶活性正常时,鱼藤酮抑制了呼吸频率,复合物I活性显著改变。透化的血小板里的复合物I基质的增加完全恢复了线粒体的呼吸功能。线粒体呼吸参数的变化与AD的进展不相关,除了透化的血小板里的ETS的容量。AD患者里复合物I的活性增加,复合物IV活性降低,辅酶Q10的血浆浓度减少。我们的数据表明,进入到氧化磷酸化系统的两种基质都不足,ETS复合物的功能障碍是从AD患者完整的血小板里观察到的呼吸减少的原因。复合物IV活性、完整的血小板的呼吸频率、透化的血小板的ETS的容量的分析可能描述AD初期的线粒体的功能障碍的特征。
关键词: 阿尔茨海默病,生物标志物,线粒体,血小板,呼吸链,呼吸频率。
Current Alzheimer Research
Title:Mitochondrial Respiration in the Platelets of Patients with Alzheimer’s Disease
Volume: 13 Issue: 8
Author(s): Zdeněk Fišar, Jana Hroudová, Hana Hansíková, Jana Spáčilová, Petra Lelková, László Wenchich, Roman Jirák and Martina Zvěřová, Jiří Zeman, Pavel Martásek, Jiří Raboch
Affiliation:
关键词: 阿尔茨海默病,生物标志物,线粒体,血小板,呼吸链,呼吸频率。
摘要: 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.
Export Options
About this article
Cite this article as:
Zdeněk Fišar, Jana Hroudová, Hana Hansíková, Jana Spáčilová, Petra Lelková, László Wenchich, Roman Jirák and Martina Zvěřová, Jiří Zeman, Pavel Martásek, Jiří Raboch , Mitochondrial Respiration in the Platelets of Patients with Alzheimer’s Disease, Current Alzheimer Research 2016; 13 (8) . https://dx.doi.org/10.2174/1567205013666160314150856
DOI https://dx.doi.org/10.2174/1567205013666160314150856 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Related Journals
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Theories and Treatment of Drug Dependency: A Neurochemical Perspective
Current Molecular Pharmacology Homocysteine in Neurology: From Endothelium to Neurodegeneration
Current Nutrition & Food Science Identification of Disease States and Response to Therapy in Humans by Utilizing the Biomarker EGFR for Targeted Molecular Imaging
Current Protein & Peptide Science Dental Stem Cell in Tooth Development and Advances of Adult Dental Stem Cell in Regenerative Therapies
Current Stem Cell Research & Therapy Cigarette Smoke-Induced Oxidant Stress in the Lung, the Unfolded Protein Response, and COPD
Current Respiratory Medicine Reviews Tumor Stroma Manipulation By MSC
Current Drug Targets Mitochondrial Pharmaceutics: A New Therapeutic Strategy to Ameliorate Oxidative Stress in Alzheimer’s Disease
Current Aging Science From Na+/K+-ATPase and Cardiac Glycosides to Cytotoxicity and Cancer Treatment
Anti-Cancer Agents in Medicinal Chemistry Novel Chemotherapeutic Agents - The Contribution of Scorpionates
Current Medicinal Chemistry Trafficking and Signaling of G Protein-Coupled Receptors in the Nervous System: Implications for Disease and Therapy
CNS & Neurological Disorders - Drug Targets Molecular Targeted Approaches for Treatment of Pancreatic Cancer
Current Pharmaceutical Design Alternative Splicing and Tumor Progression
Current Genomics Dynamic Expression of MicroRNAs (183, 135a, 125b, 128, 30c and 27a) in the Rat Pilocarpine Model and Temporal Lobe Epilepsy Patients
CNS & Neurological Disorders - Drug Targets Kappa Receptor Bivalent Ligands
Current Topics in Medicinal Chemistry Anaplastic Lymphoma Kinase Inhibitors in Non-Small Cell Lung Cancer
Current Drug Targets Modulating Mitochondria-Mediated Apoptotic Cell Death through Targeting of Bcl-2 Family Proteins
Recent Patents on DNA & Gene Sequences DNMT3B Promoter Polymorphisms and Risk of Late Onset Alzheimer’s Disease
Current Alzheimer Research Biophysical Characterization of the Nucleoside Diphosphate Kinase of Leishmania major and Effect of the P95S Mutation
Protein & Peptide Letters Peptide Receptor Radionuclide Therapy with Somatostatin Analogues in Neuroendocrine Tumors
Anti-Cancer Agents in Medicinal Chemistry Editorial (Hot Topic: Survival Signaling Through Focal Adhesion Kinase in Tumors)
Anti-Cancer Agents in Medicinal Chemistry