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Subcellular insight into cholesterol-mediated proliferation of the tick cell line
KROPÁČKOVÁ, Sára
Arthropods, including ticks, are not able to synthetise cholesterol de novo. However, cholesterol is an essential component of their cell membranes and serves as a precursor for the synthesis of steroid hormones. In this thesis, I looked at the biological function of exogenous cholesterol on the tick Ixodes ricinus cell line IRE/CTVM19. I verified the need for cholesterol supplementation in the growth medium for proper cell proliferation. Cellular proliferation was stimulated by cholesterol and not by other sterols (ergosterol, sitosterol). We further explored the two assumed aforementioned cholesterol cellular roles, but also investigated the role of cholesterol as a signal molecule: The effect of cholesterol sensing is described on the tick cell level, as well as on the level of the whole organism, using the ex vivo feeding system of ticks. This work provides novel insights into the cholesterol biology of ticks and tick cells, increasing our understanding of tick-host blood molecules' interaction.
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The role of new profibrotic molecules in the pathogenesis of systemic sclerosis.
Šumová, Barbora ; Šenolt, Ladislav (advisor) ; Funda, David (referee) ; Soukup, Tomáš (referee)
Systemic sclerosis (SSc) is immune-mediated fibrotic disease of unknown aetiology. Among the dominant pathogenic manifestations of SSc belong vascular changes, production of autoantibodies, activation of innate and adaptive immune responses and fibrotic processes. Transforming growth factor beta (TGF-β) has been identified as a central profibrotic factor stimulating fibroblasts to produce collagen. There are, however, a number of other mediators involved in the pathogenesis of SSc. Mutual activation and amplification of these molecules and their cascades may be a central mechanism of the SSc pathogenesis. Hedgehog (Hh) canonical signalling pathway plays an important role in the development and progression of fibrotic diseases. Expression of Hh target genes can be regulated through a canonical or non-canonical signalling cascade. The non-canonical activation of GLI transcription factors by TGF-β has not yet been investigated in SSc. The substantial part of this thesis is focused on the study of the mutual interaction of TGF-β and Hh signalling pathway. In vitro analysis confirmed TGF- β/SMAD3 dependent activation of GLI2 in dermal fibroblasts. Fibroblasts specific knockout of GLI2 prevented the development of experimental fibrosis in vivo. Combined targeting of canonical and non-canonical Hh...
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Rodina proteinů obsahujících sterol-sensing doménu
Ditrychová, Karolína ; Zíková, Martina (advisor) ; Fafílek, Bohumil (referee)
1. Abstract Sterol sensing domain (SSD) is a putative transmembrane region consisting of 5 helices and in few cases it was shown that it interacts with cholesterol. Proteins containing this domain play a role in many cellular pathways connected to cholesterol. It was first described in a study of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase). It is an enzyme playing role in cholesterol biosynthesis and its transcription is regulated by sterol regulatory element binding protein cleavage activating protein (SCAP). HMG-CoA reductase and SCAP were the first proteins where SSD was recognized. After that, other proteins were described; one more protein functioning in cholesterol biosynthesis was described as containing SSD - 7-dehydrocholesterol reductase. Also two proteins playing role in cholesterol endocytosis - Niemann-Pick type C 1 liked 1 - and in its efflux from lysosomes - Niemann-Pick type C 1 - were recognized. Furthermore, proteins playing role in Hedgehog signalling Patched, Patched-related and Dispatched were found as SSD containing structures. In the end, tumour-suppressor gene TRC8 was also recognized as member of SSD family. In this text, structure and function of these proteins is summarized. Key words: sterol sensing domain, Hedgehog signalling pathway, sterol binding protein,...
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