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The role of PCr/CK shuttle in adult rat myocardium under normoxic hypoxic conditions
Honcová, Lada ; Žurmanová, Jitka (advisor) ; Novotný, Jiří (referee)
The creatine kinase (CK) is an important enzyme of cell energy metabolism in excitable tissue. It occurs in four isoforms. Two cytosolic isoforms are functional in mono and hetero dimers and two mitochondrial isoforms reach tetramer and octamer forms. Its primary function is the regeneration of ATP close to ATPases and phosphocreatine pool from creatine and ATP, which gives its posphate in places of acute requirements of high energy demand. Dysfunction of CK is connected with heart, muscle and neurological diseases and CK is often used as a clinical indicator. This work is focused to the role of CK in energy metabolism of hypoxia adapted myocardium. CK thaks to production of ADP in mitochondria decreases a membrane potential as well as production of reactive oxygen species (ROS). ROS cause most of damage during ischemic heart disease and infarct of myocardium. That`s why cardioprotective effects and CK itself during hypoxia are investigated.
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Potential role of opioids in neuroprotection
Gebauer, Martin ; Novotný, Jiří (advisor) ; Rudajev, Vladimír (referee)
The opioids have been used by mankind for more than two millennia, but effect and mechanism of their action on the cells has been unveiling in the last few decades. The mechanism itself is often still unknown, but its effect is observed only. There are several groups of opioid receptors which are able to bind opioids. These groups are characterized by their differe nt affinity to opioids, in some cases by their different effects on cells and by their representation in the various areas in the CNS. Thus, the effects induces by these opioid are very different in many cases. This thesis summarizes the current knowledge about coronary heart disease and the potential of opioids for the prevention and their effect during ischemia, also summarizes the effects of morphine on the CNS. During ischemia δ-opioid receptors play a major role, because they inhibit or block the proapoptotic effects of ischemia on many levels. These receptors are also involved in inducing and maintaining the animal hibernation and protect animal's body against very harmful effects of hibernation, e.g lack of oxygen and nutrients. Morphine is opioid which has been used as anesthetic for longest time. It is well-known opioid and it has the most known derivates. This thesis also summarizes most significant effects of morphine on...
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Opioid receptors and their signaling system in the myocardium
Ladislav, Marek ; Novotný, Jiří (advisor) ; Neckář, Jan (referee)
The main objective of this bachelor thesis is to systematically collect and sort information about opioid receptors and their signaling system in the myocardium. Heart activity is controlled mainly by adrenergic signaling, and this work therefore contains also some data concerning the characteristic and significance of other relevant receptors. For better understanding, general basic information about opioid system, especially about the receptors and their signaling, is also provided. Relatively little is known about opioid receptors in the myocardium even though these receptors may have an important role especially in various pathophysiological conditions. There can be several reasons for this. The possibility of further characterization of opioid receptors in the myocardium is rather difficult due to the relatively small number of these receptors in heart tissue. The situation is somewhat complicated also by some differences in the modulation of cardiac function among different species. The complete molecular mechanism by which opioid receptors act on the myocardium has not yet been fully uncovered. Especially in the case of humans this knowledge can be crucial, because these receptors and their ligands could be used for medical purposes.
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Molecular physiology of opioid receptors
Valný, Martin ; Novotný, Jiří (advisor) ; Hejnová, Lucie (referee)
The opioid receptors (OR) belong to the family of G protein-coupled receptors (GPCRs). ORs mediate the effects of the opioids, leading primarily to inhibition of neuroexcitability, predominantly through the class of the inhibitory G proteins Gi/Go. Cloning of ORs confirmed the existence of four subtypes of ORs, which mediate effects of different classes of opioid ligands. The major aim of this work is to summarize the current knowledge about characteristics and function of ORs at the molecular level. Acute exposition of ORs to their agonists results in activation of the signaling cascades that trigger mechanisms leading to analgesia. Chronic exposition of ORs to their agonists leads to desensitization and internalization of the receptors and induces adaptive changes in signal transduction system that suppresses the opioid action, and may result in the development of opioid tolerance and dependence. Although a big progress has been made in the field of understanding the molecular mechanisms of the OR-mediated signaling, there are still a lot of unresolved questions that are necessary to answer.
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Oxidative stress as the possible outcome of opioid treatment
Böhmová, Barbora ; Novotný, Jiří (advisor) ; Žurmanová, Jitka (referee)
Free radicals and reactive oxygen species are continuously formed in all aerobic organisms. They may be implicated in ethiology of some diseases such as cancer, atherosclerosis, rheumatoid arthritis, liver, renal, cardiovascular, and neurodegenerative diseases and premature aging. Free radicals and reactive oxygen species can also cause oxidative damage to important cellular components - proteins, lipids, and DNA. Cells are equipped with antioxidant systems to neutralize these radicals. The antioxidant system includes some vitamins (ascorbic acid, α-tocopherol, β-carotene) and enzymes, e.g., superoxide dismutase converting superoxide radical to hydrogen peroxide and molecular oxygen or catalase destroying H2O2. Another important H2O2-removing enzyme in human cells is glutathione peroxidase. Reduced activity of antioxidants leads to excessive production of free radicals resulting in oxidative stress. Opioids belong among pro-oxidants (chemicals inducting oxidative stress). Opioids can decrease activity of antioxidant enzymes and generate reactive oxygen species. The aim of this bachelor thesis is to gather information regarding the opioid ability to elicit oxidative stress. It briefly summarizes our current knowledge about opioids, oxidative stress, free radicals and antioxidants. Key words Opioids,...
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Antinociceptive and neurotoxic effects of opioids
Moravcová, Radka ; Novotný, Jiří (advisor) ; Hejnová, Lucie (referee)
2. Abstract The curative actions of opioids have been known over two millenia. However, the mechanisms of their analgesic effects were only decoded in the last 20 years. There are 3 main types of opioid receptors (µ, κ, δ), that are together with the opioid peptidic system involved in antinociceptive processes and are widespread in the nervous system. Calcium plays a very important role in the pain perception and antinociception. Changes in its concentration are crucial for the neurotransmitter release. The relationship between the analgetic actions of opioids and the availability of Ca2+ in the CNS is explained in the way that, decreasing extracellular concentration of Ca2+ and/or by passaging through the membrane, antinociception will increase. Opioid analgesic effects are limited by their relatively high ability to create tolerance or addiction. Since these effects only result from heavy doses and long-term usage, severe complications should not arise during the right usage of these drugs. However, opioids can also have neurotoxic effects. The opioid-induced toxicity occurs in case when opioids release toxic metabolites during the process of their degradation in the liver. The neurotoxicity can be induced by the oxidation of the double bond in the opioid's chemical structure, thus producing free radicals...
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Role of apoptosis in the mechanism of opioid effect
Moravcová, Simona ; Novotný, Jiří (advisor) ; Ostašov, Pavel (referee)
2. Abstract Opioids have been used as effective analgesics for many years. The worst problem is, however, their adverse effects and potential addiction. There are three known types of opioid receptors that differ mainly in their sensitivity to different opioids and their distribution in the CNS. This work also deals with apoptosis. Apoptosis is an important process not just in the embryonic development, e.g. for the right differentation of fingers and toes, but also in the adulthood, e.g. to suppress tumour formation. Whereas an apoptotic pathway can be initiated in many different ways, there is only one mechanism that actually causes the death of a cell. It is important for the cell death and division to be in balance. The breach of this balance may result in pathologic effects. This work summarizes the effects of opioids in connection with apoptosis. The main object of the research of this relationship was morphine which has both pro-apoptotic and anti-apoptotic effects. Another two frequently investigated opioids are methadone and heroin. Heroin is mainly used in the studies researching the impact of this highly addictive opioid on the apoptosis and embryonic development. Keywords: opioids, opioid receptors, G-proteins, apoptosis, morphine
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Endogenous opioids and their physiological significance
Jandová, Gabriela ; Novotný, Jiří (advisor) ; Rudajev, Vladimír (referee)
This study examines the influence of endogenous opioid system on physiological processes. Opioid substances and their receptors are located not only in central but also in peripheral nervous systems, as well as in other tissues. Endogenous opioids are produced in the body and influence a wide-range of physiological functions. They are regulators of pain, emotions, breathing, memory, homeostatic functions, etc. Due to their diversity and variety of effects, they may have many possible medical uses, whether in the field of cardiology, anesthesiology or psychiatry. Since the opioid system influences many physiological processes, the understanding of its properties and functioning is prerequisite for deeper study of those processes. Therefore, the study of opioid system and new discoveries in this field receive a great deal of attention nowadays. Key words: Opioid system, endogenous opioids, receptors, nervous system, physiological functions, pain, emotions, breathing, memory, homeostasis
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Study of metabolic syndrome in mice model: roles of dietary lipids, adipose tissue and AMP-activated protein kinase
Medříková, Daša ; Kopecký, Jan (advisor) ; Houštěk, Josef (referee) ; Novotný, Jiří (referee)
Obesity and associated metabolic disorders, e. g. metabolic syndrome, represent a considerable health threat for modern society. Due to sedentary lifestyle, high caloric intake and changes in composition of diet, prevalence of obesity is increasing worldwide. One of the possible causes contributing to higher prevalence of obesity in recent population could be the change of fatty acids (FA) composition of dietary lipids, with the shift in the content of n-6 and n-3 FA toward n-6 FA. In contrast to n-6 FA, n-3 FA are known for their anti-atherogenic, anti-obesogenic and anti-inflammatory properties. In our experiments in mice, the capability of naturally occurred and chemically modified n- 3 long chain polyunsaturated fatty acids (LC-PUFA) in prevention and reversal of specific parts of metabolic syndrome was demonstrated. A specific chemical derivative of docosahexaenoic acid was proven to be very effective in preventing and improving metabolic conditions of animals exposed to high-fat (HF) diet challenge. Further, the involvement of AMP-activated protein kinase (AMPK), a master regulator of lipid metabolism, in skeletal muscle thermogenesis induced by HF-feeding was investigated. Activation of AMPK in the HF-fed mice is most possibly caused by increased leptin levels and represents an important link...
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Scattering of the electroweak vector bosons
Morávek, Petr ; Hořejší, Jiří (advisor) ; Novotný, Jiří (referee)
In the present work we study the scattering of vector gauge bosons in the framework of higher dimensional theory of Kaluza-Klein type. This work provides an instructive introduction to the given problematics with all technical details of the relevant calculations. The basic ideas of the theory are demonstrated on a set of simple models. Particular attention is paid to the selection of consistent boundary conditions using the variational principle of least action, gauge invariance and tree-level unitarity of longitudinal gauge bosons scattering.
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