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Cell senescence in aging, cell stress and chemoresistance
Andrašková, Tereza ; Vokřál, Ivan (advisor) ; Macháček, Miloslav (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Tereza Andrašková Supervisor: Prof. Dr. Alexandra K. Kiemer and PharmDr. Ivan Vokřál, PhD. Title of diploma thesis: Cell senescence in aging, cell stress, and chemoresistance The process of biological aging is connected with a loss of tissue function leading to the various pathologies, including cardiovascular diseases and cancer. Cellular senescence, the phenomenon characterized by permanent cell cycle arrest triggered by endogenous or exogenous stress plays a significant role in age-related metabolic diseases development. Senescent endothelial cells have been found in atherosclerotic plaque and due to the inflammation-inducing factors participate to its progression. Nevertheless, by triggering antiproliferative reaction, senescence may also have a potential as a cancer suppressor. The aim of this work was to establish assay determining senescence with different origins and subsequently, to analyse compounds with a potential to reduce H2O2-induced senescence as well as factors, which may be altered in the senescent phenotype. Senescence-associated β- galactosidase (SA-β-gal) assay in primary human endothelial cells revealed the senescence-inhibiting ability of statins and curcumin in contrast...
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Cell senescence with a focus on telomerase theory
Laštůvková, Viktorie ; Tlapáková, Tereza (advisor) ; Hanus, Robert (referee)
Cell senescence is an irreversible state in which the cell cycle ends. The cell remains metabolically active, but its physiological functions are limited. Cell cycle arrest is a response to the action of a number of factors, most of which affect the secondary structure of DNA in various ways and cause damage to it. Other initiators of cell entry into the senescent state are oncogenes and chemotherapeutics. One of the best studied factors, which is also in a way the "fairest", is the shortening of the telomere. Telomeres are non-coding regions of DNA at the chromosome ends that shorten slightly with each division of the cell. If the cell does not have mechanisms to compensate for this loss, the Hayflick limit is reached after a certain time. In general, senescence can be considered as a protective mechanism to prevent DNA damage pathologies. However, the presence of senescent cells in tissues is often ambivalent, accumulates with age, and can cause many degenerative diseases. The senescent phenotype includes a wide range of signs such as changes in cell size and shape, increased granularity, or altered range of expressed genes. A significant phenomenon of senescent cells is the secretion of biologically active factors contributing to physiological or pathological changes in the organism. Key words:...
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