Q57027886
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Pyruvate carboxylase (PC) is a mitochondrial, biotin-containing enzyme catalyzing the ATP-dependent synthesis of oxaloacetate from pyruvate and bicarbonate, with a critical anaplerotic role in sustaining the brain metabolism. Based on the studies performed on animal models, PC expression was assigned to be glia-specific. To study PC distribution among human neural cells, we probed the cultured human astrocytes and brain sections with antibodies against PC. Additionally, we tested the importance of PC for the viability of cultured human astrocytes by applying the PC inhibitor 3-chloropropane-1,2-diol (CPD). Our results establish the expression of PC in mitochondria of human astrocytes in culture and brain tissue and also into a subpopulation of the neurons in situ. CPD negatively affected the viability of astrocytes in culture, which could be partially reversed by supplementing media with malate, 2-oxoglutarate, citrate, or pyruvate. The provided data estimates PC expression in human astrocytes and neurons in human brain parenchyma. Furthermore, the enzymatic activity of PC is vital for sustaining the viability of cultured astrocytes.
- MeSH
- astrocyty * metabolismus MeSH
- kyselina pyrohroznová metabolismus MeSH
- lidé MeSH
- mozek metabolismus MeSH
- neurony metabolismus MeSH
- pyruvátkarboxylasa * metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Postihnutie hornej časti tráviaceho traktu u pacientov s Parkinsonovou chorobou sa v literatúre zmieňuje menej často než postihnutie jeho dolnej časti. Jeho klinický význam je ale značný, pretože dysfágické ťažkosti významne znižujú kvalitu života pacientov a môžu viesť k život ohrozujúcim komplikáciám. Napriek tomu, že klinické ťažkosti sa spájajú skôr s pokročilejšími štádiami ochorenia, poruchy motility pažeráka ako dôsledok Parkinsonovej choroby možno pomocou pažerákovej manometrie s vysokým rozlíšením zachytiť oveľa skôr. Autori v článku popisujú základné princípy diagnostického manažmentu dysfágie u pacientov s Parkinsonovou chorobou a v klinickej časti prezentujú analýzu vlastného súboru pacientov. Zistili, že nešpecifické a rôznorodé poruchy motility sú prítomné u väčšiny pacientov aj v neprítomnosti dysfágických symptómov. V experimentálnej časti sme načrtli nové možnosti diagnostických postupov pomocou najmodernejších metodík detekcie patologických foriem alfa-synukleínu a pokročilých mikroskopických metód.
Involvement of the upper part of the gastrointestinal tract in patients with Parkinson disease is reported less frequently than the involvement of the lower part. Its clinical impact is, however, substantial because dysphagic symptoms considerably decrease the quality of life and may lead to life threatening complications. Even though the clinical symptoms related to esophageal motility disorders as a result of Parkinson disease are more common in the advanced stages of the disease, these could be diagnosed much earlier using high resolution manometry. The authors describe the basic principles of diagnostic management of dysphagia in patients with Parkinson disease and in the clinical part they present an analysis of their patient cohort. They found out that nonspecific and diverse motility disorders are present in most patients, even without dysphagic symptoms. In the experimental part, we outlined new possibilities for diagnostic procedures using the most up-to-date methods for the detection of pathological forms of alpha-synuclein and advanced microscopic methods.
Numerous pathological changes of subcellular structures are characteristic hallmarks of neurodegeneration. The main research has focused to mitochondria, endoplasmic reticulum, Golgi apparatus, lysosomal networks as well as microtubular system of the cell. The sequence of specific organelle damage during pathogenesis has not been answered yet. Exposition to rotenone is used for simulation of neurodegenerative changes in SH-SY5Y cells, which are widely used for in vitro modelling of Parkinson ́s disease pathogenesis. Intracellular effects were investigated in time points from 0 to 24 h by confocal microscopy and biochemical analyses. Analysis of fluorescent images identified the sensitivity of organelles towards rotenone in this order: microtubular cytoskeleton, mitochondrial network, endoplasmic reticulum, Golgi apparatus and lysosomal network. All observed morphological changes of intracellular compartments were identified before alphaS protein accumulation. Therefore, their potential as an early diagnostic marker is of interest. Understanding of subcellular sensitivity in initial stages of neurodegeneration is crucial for designing new approaches and a management of neurodegenerative disorders.
- MeSH
- apoptóza MeSH
- insekticidy toxicita MeSH
- lidé MeSH
- mikrotubuly účinky léků metabolismus patologie MeSH
- mitochondrie účinky léků metabolismus patologie MeSH
- nádorové buněčné linie MeSH
- NADPH-oxidasy metabolismus MeSH
- neuroblastom komplikace MeSH
- neurodegenerativní nemoci etiologie metabolismus patologie MeSH
- rotenon toxicita MeSH
- viabilita buněk MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Parkinson's disease (PD) is most commonly manifested by the presence of motor symptoms. However, non-motor symptoms occur several years before the onset of motor symptoms themselves. Hallmarks of dysfunction of the respiratory system are still outside the main focus of interest, whether by clinicians or scientists, despite their indisputable contribution to the morbidity and mortality of patients suffering from PD. In addition, many of the respiratory symptoms are already present in the early stages of the disease and efforts to utilize these parameters in the early diagnosis of PD are now intensifying. Mechanisms that lead to the development and progression of respiratory symptoms are only partially understood. This review focuses mainly on the comparison of respiratory problems observed in clinical studies with available findings obtained from experimental animal models. It also explains pathological changes observed in non-neuronal tissues in subjects with PD.
- MeSH
- lidé MeSH
- mechanika dýchání fyziologie MeSH
- neurodegenerativní nemoci diagnóza epidemiologie patofyziologie MeSH
- Parkinsonova nemoc diagnóza epidemiologie patofyziologie MeSH
- poruchy dýchání diagnóza epidemiologie patofyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Parkinson's disease (PD) is currently the second most common neurodegenerative disorder in the world. Major features of cell pathology of the disease include the presence of cytoplasmic inclusions called Lewy bodies, which are composed of aggregated proteins. The presence of Lewy's body is associated with more advanced stages of the disease when considering irreversible changes. Precise identification of the disease stage at a cellular level presents the critical tool in developing early diagnostics and/or prevention of PD. The aim of our work is to introduce sensitive microscopic analysis in living cells, focused on initial intracellular changes and thus capable to detect earlier stages of the disease.
- MeSH
- alfa-synuklein metabolismus MeSH
- biologické markery metabolismus MeSH
- buněčná inkluze metabolismus patologie MeSH
- intracelulární tekutina metabolismus MeSH
- lidé MeSH
- membránový potenciál mitochondrií fyziologie MeSH
- mitochondrie metabolismus patologie MeSH
- NAD metabolismus MeSH
- nádorové buněčné linie MeSH
- optické zobrazování metody MeSH
- Parkinsonova nemoc metabolismus patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
