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The Role of Dipeptidyl Peptidase-IV in Glioma Cell Growth
Bušek, Petr ; Šedo, Aleksi (advisor) ; Trka, Jan (referee) ; Konvalinka, Jan (referee)
Dipeptidyl peptidase-IV (DPP-IV, CD26, EC 3.4.14.5) is a widely expressed serine protease that by limited proteolysis regulates a number of biologically active peptides including a number of mitogenic peptides involved in cancer development. Deranged DPP-IV expression and/or enzymatic activity has been reported in a number of tumors, and could lead to altered signaling and biological function of its substrates. Changes in DPP-IV expression were observed in glioma cell lines in association with differentiation, and recently also in malignant gliomas in vivo. In addition, DPP-IV substrates substance P (SP) and stromal cell derived factor-1 (SDF-1) that trigger growth promoting intracellular signaling cascades in glioma cells have strongly been implicated in the pathogenesis of gliomas. The aim of this study was (i) to investigate the effects of DPP-IV on the signaling of its biologically active substrates that promote the malignant phenotype of glioma cells, and (ii) to assess the effects of DPP-IV on the growth, migration and adhesion of human glioma cells. Using transfected glioma cell lines (U373CD26, T98GCD26, U87CD26) with mifepristone-inducible DPP-IV expression, we demonstrate that DPP-IV overexpressing T98GCD26 cells can cleave SP and thus abrogate its ability to trigger calcium signaling in U373...
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Metabotropic glutamate receptors: mechanism of activation
Hlaváčková, Veronika ; Blahoš, Jaroslav (advisor) ; Vyklický, Ladislav (referee) ; Martásek, Pavel (referee) ; Konvalinka, Jan (referee)
Any living organism receives constantly many signals that have to be evaluated and weighted to respond in an appropriate way. To perform all functions needed for precise control of homeostasis and for communication with the surrounding environment, signals coming from the outside are recognized and transferred into modulation of intracellular signaling cascades. These mediate response to the extracellular stimulus as well as intercellular communication. Cell communication is mediated by several types of receptors, located either intracellularly (including nuclear receptors) that modulate gene transcription and receptors localized on plasma membrane. Cell membrane receptors are transmembrane proteins that are divided into three superfamilies according to their structure and principles of signal transduction. These are ion channel-linked receptors, enzyme-linked receptors and G-protein-coupled receptors (GPCRs). GPCRs comprise the biggest family of membrane receptors and are one of the largest gene families in general. They are encoded by about 1% of genes in mammals. Many of them bind sensory ligands (rhodopsin, taste and olfactory receptors), but others also recognize ions, amino acids, nucleotides, peptides and large glycoproteins (1). They play a crucial role in such distant physiological functions as...
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Methods of measurement of bone density
Konvalinka, Jan ; Valášek, Jiří (referee) ; Marcián, Petr (advisor)
This bachelor's thesis focuses on methods for measuring bone density and consequences of changes in bone density on biomechanical properties of bone tissue. In first part are described methods of bone densitometry, especially radiological methods, which are currently most widely used. Second part focuses on measuring bone density from CT images (hog femur bone, healthy and damaged human femur bone and lumbar vertebra) using software ROI Analysis. Third part discusses influence of changes in bone density on strain-stress quantities of trabecular bone. For the assessment was created 2D computational model of hip using FEM.
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Vazba fenylnorstatinového inhibitoru na proteázu HIV-1: geometrie, protonace a interakce kapes podřadných míst analyzované při atomovém rozlišení
Brynda, Jiří ; Řezáčová, Pavlína ; Fábry, Milan ; Hořejší, Magdalena ; Štouračová, Renata ; Sedláček, Juraj ; Souček, Milan ; Hradilek, Martin ; Lepšík, Martin ; Konvalinka, Jan
The x-ray structure of a complex of HIV-1 protease (PR) with a phenylnorstatine inhibitor Z-Pns-Phe-Glu-Glu-NH2 has been determined at 1.03 A, the highest resolution so far reported for any HIV PR complex. The inhibiot shows subnanomolar Ki values for both the wild-type PR and the variant representing one of the most common mutations linked to resistance development. The structure displays a unique pattern of hydrogen bonding to the two catalytic aspartate residues. The high resolution permints to assess the donor/acceptor relations of this hydrogen bonding and to indicate a proton shared by the two catalytic residues. Structural mechanism for the unimpaired inhibition of the protease Val82Ala mutant is also suggested, based on energy calculations and analyses
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