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Mitochondrial transfer and its role in regenerative properties of mesenchymal stem cells
Jaborová, Natálie ; Krulová, Magdaléna (advisor) ; Nahácka, Zuzana (referee)
Mitochondrial transfer represents a form of intercellular communication. In this process, mitochondria are delivered from the donor cell to the recipient cell through several structures. The transfer of mitochondria is observed under pathological and physiological conditions and is accompanied by specific signaling. Mitochondria uptake by injured cells promotes tissue regeneration. This bachelor thesis discusses general knowledge of mitochondrial transfer focusing on mesenchymal stem cells (MSCs) as a donor cell type. Furthermore, the regenerative effect of MSC-derived mitochondria transfer to cells damaged by various pathologies is summarized. In this regard, MSCs have significant therapeutic potential that could be used in future clinical strategies for a number of diseases. Keywords: mitochondria, transfer, mesenchymal stem cells, regeneration
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Canonical and non-canonical signalling triggered by activated TRAIL receptors in human cells
Nahácka, Zuzana ; Anděra, Ladislav (advisor) ; Rudolf, Emil (referee) ; Vondráček, Jan (referee)
TRAIL ligand can trigger apoptosis of permissive human cells via engagement of its two pro- apoptotic receptors TRAIL-R1 (DR4) and TRAIL-R2 (DR5). Its ability to induce apoptosis independently on p53 status and to selectively kill cancer cells in vitro and in vivo made this ligand an attractive target in cancer research. However, acquired resistance of primary cancer cells, unsatisfactory outcome of clinical trials and recent studies arguing that TRAIL might under specific conditions promote cancer progression, opened new plethora of questions, which need to be addressed. Though both receptors DR4 and DR5 are ubiquitously expressed, different types of tumours show preference for either of the receptors. The relative participation of DR4 and DR5 in TRAIL- induced signalling is still largely unknown. To analyse TRAIL receptor-specific signalling, I prepared Strep-tagged, trimerised variants of recombinant human TRAIL ligands with high affinity for either DR4 or DR5 receptor. Using these receptor-specific ligands, I examined a contribution of individual pro-apoptotic receptors to TRAIL-induced signalling pathways. I found that in TRAIL resistant colorectal HT-29 cells but not in pancreatic PANC-1 cancer cells, DISC formation and initial caspase-8 processing proceeded comparably in both DR4- and...
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Canonical and non-canonical signalling triggered by activated TRAIL receptors in human cells
Nahácka, Zuzana
TRAIL ligand can trigger apoptosis of permissive human cells via engagement of its two pro- apoptotic receptors TRAIL-R1 (DR4) and TRAIL-R2 (DR5). Its ability to induce apoptosis independently on p53 status and to selectively kill cancer cells in vitro and in vivo made this ligand an attractive target in cancer research. However, acquired resistance of primary cancer cells, unsatisfactory outcome of clinical trials and recent studies arguing that TRAIL might under specific conditions promote cancer progression, opened new plethora of questions, which need to be addressed. Though both receptors DR4 and DR5 are ubiquitously expressed, different types of tumours show preference for either of the receptors. The relative participation of DR4 and DR5 in TRAIL- induced signalling is still largely unknown. To analyse TRAIL receptor-specific signalling, I prepared Strep-tagged, trimerised variants of recombinant human TRAIL ligands with high affinity for either DR4 or DR5 receptor. Using these receptor-specific ligands, I examined a contribution of individual pro-apoptotic receptors to TRAIL-induced signalling pathways. I found that in TRAIL resistant colorectal HT-29 cells but not in pancreatic PANC-1 cancer cells, DISC formation and initial caspase-8 processing proceeded comparably in both DR4- and...
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Canonical and non-canonical signalling triggered by activated TRAIL receptors in human cells
Nahácka, Zuzana
TRAIL ligand can trigger apoptosis of permissive human cells via engagement of its two pro- apoptotic receptors TRAIL-R1 (DR4) and TRAIL-R2 (DR5). Its ability to induce apoptosis independently on p53 status and to selectively kill cancer cells in vitro and in vivo made this ligand an attractive target in cancer research. However, acquired resistance of primary cancer cells, unsatisfactory outcome of clinical trials and recent studies arguing that TRAIL might under specific conditions promote cancer progression, opened new plethora of questions, which need to be addressed. Though both receptors DR4 and DR5 are ubiquitously expressed, different types of tumours show preference for either of the receptors. The relative participation of DR4 and DR5 in TRAIL- induced signalling is still largely unknown. To analyse TRAIL receptor-specific signalling, I prepared Strep-tagged, trimerised variants of recombinant human TRAIL ligands with high affinity for either DR4 or DR5 receptor. Using these receptor-specific ligands, I examined a contribution of individual pro-apoptotic receptors to TRAIL-induced signalling pathways. I found that in TRAIL resistant colorectal HT-29 cells but not in pancreatic PANC-1 cancer cells, DISC formation and initial caspase-8 processing proceeded comparably in both DR4- and...
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Canonical and non-canonical signalling triggered by activated TRAIL receptors in human cells
Nahácka, Zuzana ; Anděra, Ladislav (advisor) ; Rudolf, Emil (referee) ; Vondráček, Jan (referee)
TRAIL ligand can trigger apoptosis of permissive human cells via engagement of its two pro- apoptotic receptors TRAIL-R1 (DR4) and TRAIL-R2 (DR5). Its ability to induce apoptosis independently on p53 status and to selectively kill cancer cells in vitro and in vivo made this ligand an attractive target in cancer research. However, acquired resistance of primary cancer cells, unsatisfactory outcome of clinical trials and recent studies arguing that TRAIL might under specific conditions promote cancer progression, opened new plethora of questions, which need to be addressed. Though both receptors DR4 and DR5 are ubiquitously expressed, different types of tumours show preference for either of the receptors. The relative participation of DR4 and DR5 in TRAIL- induced signalling is still largely unknown. To analyse TRAIL receptor-specific signalling, I prepared Strep-tagged, trimerised variants of recombinant human TRAIL ligands with high affinity for either DR4 or DR5 receptor. Using these receptor-specific ligands, I examined a contribution of individual pro-apoptotic receptors to TRAIL-induced signalling pathways. I found that in TRAIL resistant colorectal HT-29 cells but not in pancreatic PANC-1 cancer cells, DISC formation and initial caspase-8 processing proceeded comparably in both DR4- and...
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