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The effect of endothelial cell proliferation on susceptibility to mitochondrially controlled apoptosis and oxidative stress.
Blecha, Jan ; Novák, Petr (advisor) ; Plecitá, Lydie (referee)
Mitochondria are multifunctional organelles playing a key role in energy metabolism and cell death induction. Mitochondria, and specifically their respiratory chain, are also the main producers of reactive oxygen species (ROS) in cells. Metabolism can be affected by the state of cellular proliferation and certain ROS-inducing agents have an antiangiogenic effect based on the preferential elimination of proliferating endothelial cells (EC). Therefore, in this work we investigated, whether mitochondria could be responsible for different sensitivity of proliferation and confluent EC to cell death. We mainly focused on systems that regulate ROS level and apoptosis: respiratory chain (ROS production), antioxidant defense (ROS detoxification) and Bcl-2 family of proteins (apoptosis regulation). First, we treated EC with functional and nonfunctional respiratory chain with various oxidative stress- and apoptosis-inducing agents and determined ROS production and susceptibility to apoptosis in proliferating and confluent cells. Our results show that functional respiratory chain greatly increases the susceptibility of proliferating cells to ROS induction and apoptosis, whereas in qiescent cells it protects against cell death. Given these findings, we assessed the activity of respiratory chain in proliferating...
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The effect of endothelial cell proliferation on susceptibility to mitochondrially controlled apoptosis and oxidative stress.
Blecha, Jan ; Novák, Petr (advisor) ; Plecitá, Lydie (referee)
Mitochondria are multifunctional organelles playing a key role in energy metabolism and cell death induction. Mitochondria, and specifically their respiratory chain, are also the main producers of reactive oxygen species (ROS) in cells. Metabolism can be affected by the state of cellular proliferation and certain ROS-inducing agents have an antiangiogenic effect based on the preferential elimination of proliferating endothelial cells (EC). Therefore, in this work we investigated, whether mitochondria could be responsible for different sensitivity of proliferation and confluent EC to cell death. We mainly focused on systems that regulate ROS level and apoptosis: respiratory chain (ROS production), antioxidant defense (ROS detoxification) and Bcl-2 family of proteins (apoptosis regulation). First, we treated EC with functional and nonfunctional respiratory chain with various oxidative stress- and apoptosis-inducing agents and determined ROS production and susceptibility to apoptosis in proliferating and confluent cells. Our results show that functional respiratory chain greatly increases the susceptibility of proliferating cells to ROS induction and apoptosis, whereas in qiescent cells it protects against cell death. Given these findings, we assessed the activity of respiratory chain in proliferating...
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The role of CSL proteins in oxidative stress response of Schizosaccharomyces pombe
Tvarůžková, Jarmila ; Převorovský, Martin (advisor) ; Rallis, Charalampos (referee)
Oxidative stress represents a complex and intensely studied phenomenon tightly linked to a range of human diseases, and to aging in many organisms. A plethora of key cellular regulators, including the Notch signaling pathway, have been recently described to respond to the cellular redox status. We have characterized the role of CSL (CBF1/Su(H)/LAG-1) proteins, the effectors of Notch signaling pathway in metazoa, in oxidative stress response in fission yeast. Schizosaccharomyces pombe contains two CSL paralogs, Cbf11 and Cbf12, that have antagonistic functions in the regulation of cell cycle and cellular adhesion. Both proteins are able to bind the canonical CSL motif and activate transcription and, thus, function as genuine CSL transcription factors. We have determined that the strain lacking cbf11 is resistant to hydrogen peroxide but not to menadione, a source of superoxide anion radical. Using double knock-outs to assess genetic interactions we have revealed that the resistance of cbf11 knock-out is dependent on the antioxidants catalase and sulfiredoxin. Genes encoding these antioxidants are under transcriptional control of the Sty1 MAP kinase pathway and the Pap1 transcription factor which are also required for the resistance of Δcbf11 cells. Cbf12 is believed to play only a minor role in...
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