National Repository of Grey Literature 4 records found  Search took 0.00 seconds. 
Protein profiling, metabolic enzymes and transmembrane signaling in the heart of spontaneously hypertensive SHR-Tg19 rat
Manakov, Dmitry ; Novotný, Jiří (advisor) ; Kuncová, Jitka (referee) ; Kalous, Martin (referee)
Cardiovascular diseases account for the majority of deaths both worldwide and in the Czech Republic. Main factors contributing heart disease development, aside age and sex, are obesity, high blood pressure and high blood cholesterol and triglyceride levels. Spontaneously hypertensive rat (SHR) was developed and used for search of genetic determinants of these traits. This commonly used rat model develops hypertension, dyslipidemia, and insulin resistance naturally which is caused by aberrant Cd36 fatty acid translocase gene. Previous studies have shown that rescue of Cd36 performed in the transgenic SHR-Tg19 strain enhances cardiac beta-adrenergic system, slightly increases heart mass and leads to higher susceptibility to arrhythmias. The present thesis had two main aims: 1) To investigate whether and how a transgenic rescue of Cd36 in SHR affects protein composition, mitochondrial function and activity of selected metabolic enzymes of the heart. 2) To study the expression and distribution of selected components of beta-adrenergic signaling system in lipid raft isolated form membranes using the TX-100 detergent. We set to compare two commonly used proteomic approaches, 2D electrophoresis with MALDI-TOF mass spectrometry and label-free LC-MS. The results did not reveal any overlap between...
Deletions in human mitochondrial DNA and causes of their formation
Zdobinský, Tomáš ; Tesařová, Markéta (advisor) ; Manakov, Dmitry (referee)
Mitochondria are organelles of eukaryotic cells that primarily provide energy metabolism, but also participate in metabolic processes such as biosynthesis of amino acids, heme groups, Fe-S clusters etc. Mitochondrial disorders represent heterogeneous group of diseases which can occur in both child and adult life. They affect various tissues and organs in different ways, most often manifesting themselves as disorders of nervous system, skeletal muscle, liver, kidneys or endocrine system. Mitochondrial DNA deletions contribute to pathogenesis of many of those diseases and they are a symptom of several defined syndromes. They most likely arise as a result of replication stalling resulting in a double strand break of DNA. This can be caused primarily by pathogenic changes in replication apparatus and nucleotide metabolism proteins. The aim of this work is to summarize the knowledge about mitochondria and structure and replication of their genome, but also to create a summary of the most important proteins whose mutation leads to mitochondrial diseases accompanied by deletions in mtDNA and to outline the mechanism by which they arise.
Glial cells and their role in Alzheimer disease
Eliášová, Barbora ; Anděrová, Miroslava (advisor) ; Manakov, Dmitry (referee)
Alzheimer's disease is a neurodegenerative disorder, affecting mostly elderly people. It causes memory impairment and modifies the ability to talk, learn and make decisions. These are gradually getting worse until the patient loses them completely. Alzheimer's is the most common form of dementia worldwide, however until these days there is no cure. The main reason for this is that mechanisms and causes of this disease are still not utterly understood. Besides the neurodegeneration caused by aggregation of βamyloid protein and hyperphosphorylated tau protein, glial cells of central nervous system play also important role in the Alzheimer's disease. Astrocytes, microglia, oligodendrocytes and recently discovered synantocytes ensure various functions necessary for correct functioning of the brain and damage of these cells can be fatal. During a neurodegenerative disorder such as Alzheimer's, they are able to improve the course of the disease but also do the contrary and aggravate it by malfunctioning or losing one or even more of their functions. Key words: Alzheimer's disease, β amyloid, tau protein, astrocytes, microglia, oligodendrocytes, synantocytes
A study of beta-adrenergic myocardial signaling in spontaneously hypertensive rat of transgenic strain SHR-Tg19
Manakov, Dmitry ; Novotný, Jiří (advisor) ; Nováková, Olga (referee)
β-Adrenergic signalization plays an important role in heart, regulating cardiac frequency and contractility. It is also involved in development of hypertension and heart hypertrophy. Spontaneous hypertensive rat strain is a common model for human essential hypertension, although the origin of blood pressure abnormalities in SHR remains unknown. Dysfunction in the regulation of fatty acid translocase Cd36 was suggested as a link to development of hypertension in SHR. Transgenic strain SHR-Tg19 (also known as SHR-Cd36) was obtained, harboring a wild type of FAT/Cd36. This thesis aimed to investigate key elements of β-adrenergic signaling in the heart of SHR-Tg19 compared to their SHR controls. Expression and distribution of β1- and β2-ARs were measured using radioligand binding and Western blot analysis along with expression of selected G proteins and expression and activity of adenylyl cyclase. Our experiments showed that there were no significant changes in the Gsα and Giα subunits expressions, along with the amount of β1-AR in both left and right ventricles, according to the Western immunoblotting, but radioligand binding showed an increase in the quantity of β-ARs, particularly β2 subtype. Alongside, an increased expression of β2- ARs was observed in the right ventricle. Different...

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