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Autophagy in the heart
Šprláková, Katarína ; Hlaváčková, Markéta (advisor) ; Tomšů, Eva (referee)
Currently, it is growing evidence that autophagy is involved in the prevention of various diseases, which of course also includes heart diseases. This thesis is therefore aimed at clarifying the role of autophagy in the heart, especially during ischemia and subsequent reperfusion. Autophagy is a physiological cellular process by which the cell maintains homeostasis by eliminating long-lived proteins and damaged organelles. The role of autophagy during ischemia/reperfusion in the heart is complex. Predominantly it functions as a pro-survival pathway, because it protects the heart from ischemia or hypoxia. However, when triggered over, which happens during reperfusion, it may lead to cell death. In the heart autophagy is activated in response to various stimuli, such as decrease in ATP and subsequent activation of AMPK, protein Bnip3, reactive oxygen and nitrogen species, the opening of mitochondrial permeability transition pore, endoplasmic reticulum stress or unfolded protein response.
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Endoplasmic reticulum stress
Červenka, Jakub ; Schierová, Michaela (advisor) ; Horníková, Lenka (referee)
The accumulation of unfolded or misfolded proteins in endoplasmic reticulum (ER) leads to ER stress and the activation of unfolded protein response (UPR). Recent studies show that ER stress or UPR are associated with many diseases such as diabetes, hepatitis type C, prion disease, different kinds of tumors or Alzheimer's, Parkinson's and Huntington's disease and also with physiological processes like cell differentiation. When UPR is activated in yeast Saccharomyces cerevisiae, Ire1 protein oligomerizes, transautophosphorylates and activates itself. After this, Ire1 cleaves HAC1 mRNA to remove an intron. The spliced form of HAC1 mRNA is translated into the Hac1 transcription factor, which induces transcription of genes for chaperones of lumen ER, proteins involved in ERAD, synthesis of lipids etc. The cell uses this to reestablish homeostasis in ER. In mammals, the UPR is more complex and except Ire1 dependent pathway, it comprises Perk and Atf6 pathways, which are missing in yeast. Nevertheless, Perk is activated and regulated by the similar mechanism as Ire1 in S. cerevisiae. In consideration of broad spectrum of methods for genetic manipulation, rapid growth and well annotated genome, the yeast S. cerevisiae is a useful model for study of general mechanisms of UPR in mammals.
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Connection between Unfolded Protein Response (UPR) and plant immunity
Kapr, Jan ; Burketová, Lenka (advisor) ; Vosolsobě, Stanislav (referee)
This bachelor thesis is concerned with the specific pathway in a response to endoplasmic reticulum stress in plant cells - the Unfolded Protein Response (UPR) and its role in plant immunity signalling. The work summarizes the main recent knowledges of molecular components of plant immunity and response to plant pathogens, focusing on important molecules that are also connected to UPR. The role of salicylic acid as a molecule on a crossroad between UPR signalling pathways and local and systemic resistence, is highlighted in this work. Recently, the phospholipids have also been shown to be important component of signaling pathways in response to biotic stress in plants and their role is also mentioned.
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Protein quality control in the secretory pathway of eukaryotic cells
Bařinková, Markéta ; Stříšovský, Kvido (advisor) ; Černý, Jan (referee)
More than 30 % of the cellular proteome enters the secretory pathway during biogenesis in eukaryotic cells. The secretory pathway then ensures that these proteins are correctly folded, undergo necessary post- translational modifications, and reach their target site in membrane organelles or outside of the cell. Since a significant number of the nascent proteins in the pathway are or become dysfunctional, the cell must possess quality control mechanisms by which to weed them out. As proteins travel through the secretory pathway they may be degraded by various pathways in the endoplasmic reticulum, Golgi apparatus, endosomes, or at the plasma membrane. These degradatory pathways utilize a number of molecules including chaperones, ubiquitin ligases, and many others. They are coordinated by a unifying principle - the unfolded protein response, which acts as a support mechanism in case the degradation pathways are overwhelmed. The study of protein quality control mechanisms is necessary as they help us understand the production of a significant portion of the cellular proteome. Furthermore, defects in these degradation pathways are linked to several human diseases such as cystic fibrosis or some neurodegenerative diseases. These protein degradation pathways have been studied for decades, but thanks to...
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The effect of HAc1p on the development of yeast colony
Maršíková, Jana ; Schierová, Michaela (advisor) ; Pichová, Iva (referee)
On solid surfaces wild strains of Saccharomyces cerevisiae form biofilm-like, structured colonies enabling them to survive long-term in hostile environments in the wild. However, the molecular mechanisms underlying the spatio-temporal development of colonies and their resistance to hostile conditions are still largely unknown. In this study, we analyzed the effect of the HAC1 gene on the colony morphology of wild strains of S. cerevisiae. The transcription factor Hac1p activates the unfolded protein response (UPR), which leads to activation of the expression of genes encoding components of the protein secretory pathway, and genes involved in stress responses in the endoplasmic reticulum (ER). The impact of HAC1 deletion is significant even under non-stress conditions and causes a radical reduction of structured colony architecture in hac1∆ strains derived from two wild S. cerevisiae strains (PORT and BR-F-Flo11p-GFP) and one laboratory ΣSh strain forming semi-fluffy or fluffy colonies. The hac1∆ strains exhibit a decreased vegetative growth rate, reduced cell attachment to the agar and an ineffective cell-cell adhesion resulting in decreased flocculation. The hac1∆ strains derived from BR-F-Flo11p-GFP contain a low level of Flo11p surface adhesin which is considered very important for the proper...
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Endoplasmic reticulum stress
Červenka, Jakub ; Schierová, Michaela (advisor) ; Horníková, Lenka (referee)
The accumulation of unfolded or misfolded proteins in endoplasmic reticulum (ER) leads to ER stress and the activation of unfolded protein response (UPR). Recent studies show that ER stress or UPR are associated with many diseases such as diabetes, hepatitis type C, prion disease, different kinds of tumors or Alzheimer's, Parkinson's and Huntington's disease and also with physiological processes like cell differentiation. When UPR is activated in yeast Saccharomyces cerevisiae, Ire1 protein oligomerizes, transautophosphorylates and activates itself. After this, Ire1 cleaves HAC1 mRNA to remove an intron. The spliced form of HAC1 mRNA is translated into the Hac1 transcription factor, which induces transcription of genes for chaperones of lumen ER, proteins involved in ERAD, synthesis of lipids etc. The cell uses this to reestablish homeostasis in ER. In mammals, the UPR is more complex and except Ire1 dependent pathway, it comprises Perk and Atf6 pathways, which are missing in yeast. Nevertheless, Perk is activated and regulated by the similar mechanism as Ire1 in S. cerevisiae. In consideration of broad spectrum of methods for genetic manipulation, rapid growth and well annotated genome, the yeast S. cerevisiae is a useful model for study of general mechanisms of UPR in mammals.
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Autophagy in the heart
Šprláková, Katarína ; Hlaváčková, Markéta (advisor) ; Tomšů, Eva (referee)
Currently, it is growing evidence that autophagy is involved in the prevention of various diseases, which of course also includes heart diseases. This thesis is therefore aimed at clarifying the role of autophagy in the heart, especially during ischemia and subsequent reperfusion. Autophagy is a physiological cellular process by which the cell maintains homeostasis by eliminating long-lived proteins and damaged organelles. The role of autophagy during ischemia/reperfusion in the heart is complex. Predominantly it functions as a pro-survival pathway, because it protects the heart from ischemia or hypoxia. However, when triggered over, which happens during reperfusion, it may lead to cell death. In the heart autophagy is activated in response to various stimuli, such as decrease in ATP and subsequent activation of AMPK, protein Bnip3, reactive oxygen and nitrogen species, the opening of mitochondrial permeability transition pore, endoplasmic reticulum stress or unfolded protein response.
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