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The effect of maternal diabetes on embryonic cardiovascular development and fetal programing
Čerychová, Radka ; Pavlínková, Gabriela (advisor) ; Nováková, Olga (referee) ; Neckář, Jan (referee)
Maternal diabetes mellitus negatively affects embryonic development and increases the risk for congenital malformations. Besides direct teratogenicity, diabetic intrauterine milieu can predispose an individual to chronic diseases later in life, including cardiovascular diseases, obesity, and diabetes mellitus, in a process termed fetal programing. Molecular mechanisms of embryonic and fetal responses to maternal diabetes are still not fully elucidated. Using mouse model, we show that maternal diabetes induces gene expression changes in the hearts of developing embryos. The most significant changes in the expression of 11 selected genes were detected at the developmental stage associated with completion of cardiac septation, myocardial mass expansion, and increased insulin production in the embryonic pancreas. These affected genes encode products involved in the epithelial-to-mesenchymal transition, a crucial process in heart development. Using immunohistochemistry, we detected increased hypoxia in the diabetes-exposed hearts at the critical stage of cardiac development. Correspondingly to increased hypoxia, the expression of hypoxia-inducible factor 1α (HIF1α) and vascular endothelial growth factor A was increased in the heart of diabetes-exposed embryos. Based on our results indicating the...
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The role of mitochondrial metabolism in initiation and adaptation to hypoxic conditions.
Rohlenová, Terezie ; Novák, Petr (advisor) ; Rohlena, Jakub (referee)
We can meet pathological hypoxia in the cases of hearth attack, ischemic stroke, but also during tumor invasion, thanks to insufficient angiogenesis. The activation of HIF- 1 factor during hypoxic conditions is crucial for the cell survival. This factor modulates energetic metabolism in favor of fast progressing glycolysis (with the contribution of glutaminolysis) which provides to cell enough ATP and "building blocks", while suppressing Krebs cycle and respiration because of shortage of oxygen. The thesis studies energetic metabolism of HepG2 cells (derived from liver carcinoma) which are cultivated in the media with various energetic substrates, i. e. glucose or galactose (always together with glutamine and pyruvate) under the hypoxic conditions (5% O2). HepG2 cells use particularly oxidative metabolism for ATP and "building blocks" production under the normoxic conditions while hypoxic environment causes metabolic shift in glycemic condition. Interestingly, cells cultured in galactose (glutamine) didn't switch the energy metabolism from oxidative to aerobic glycolysis such as cells cultivated in glucose, although HIF-1 factor was stabilized. We found that enhanced activity and integrity of mitochondria, enhanced maximal capacity and reserve capacity of respiration chain correlates with...
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The effect of maternal diabetes on embryonic cardiovascular development and fetal programing
Čerychová, Radka
Maternal diabetes mellitus negatively affects embryonic development and increases the risk for congenital malformations. Besides direct teratogenicity, diabetic intrauterine milieu can predispose an individual to chronic diseases later in life, including cardiovascular diseases, obesity, and diabetes mellitus, in a process termed fetal programing. Molecular mechanisms of embryonic and fetal responses to maternal diabetes are still not fully elucidated. Using mouse model, we show that maternal diabetes induces gene expression changes in the hearts of developing embryos. The most significant changes in the expression of 11 selected genes were detected at the developmental stage associated with completion of cardiac septation, myocardial mass expansion, and increased insulin production in the embryonic pancreas. These affected genes encode products involved in the epithelial-to-mesenchymal transition, a crucial process in heart development. Using immunohistochemistry, we detected increased hypoxia in the diabetes-exposed hearts at the critical stage of cardiac development. Correspondingly to increased hypoxia, the expression of hypoxia-inducible factor 1α (HIF1α) and vascular endothelial growth factor A was increased in the heart of diabetes-exposed embryos. Based on our results indicating the...
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|
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The effect of maternal diabetes on embryonic cardiovascular development and fetal programing
Čerychová, Radka
Maternal diabetes mellitus negatively affects embryonic development and increases the risk for congenital malformations. Besides direct teratogenicity, diabetic intrauterine milieu can predispose an individual to chronic diseases later in life, including cardiovascular diseases, obesity, and diabetes mellitus, in a process termed fetal programing. Molecular mechanisms of embryonic and fetal responses to maternal diabetes are still not fully elucidated. Using mouse model, we show that maternal diabetes induces gene expression changes in the hearts of developing embryos. The most significant changes in the expression of 11 selected genes were detected at the developmental stage associated with completion of cardiac septation, myocardial mass expansion, and increased insulin production in the embryonic pancreas. These affected genes encode products involved in the epithelial-to-mesenchymal transition, a crucial process in heart development. Using immunohistochemistry, we detected increased hypoxia in the diabetes-exposed hearts at the critical stage of cardiac development. Correspondingly to increased hypoxia, the expression of hypoxia-inducible factor 1α (HIF1α) and vascular endothelial growth factor A was increased in the heart of diabetes-exposed embryos. Based on our results indicating the...
|
|
|
The effect of maternal diabetes on embryonic cardiovascular development and fetal programing
Čerychová, Radka ; Pavlínková, Gabriela (advisor) ; Nováková, Olga (referee) ; Neckář, Jan (referee)
Maternal diabetes mellitus negatively affects embryonic development and increases the risk for congenital malformations. Besides direct teratogenicity, diabetic intrauterine milieu can predispose an individual to chronic diseases later in life, including cardiovascular diseases, obesity, and diabetes mellitus, in a process termed fetal programing. Molecular mechanisms of embryonic and fetal responses to maternal diabetes are still not fully elucidated. Using mouse model, we show that maternal diabetes induces gene expression changes in the hearts of developing embryos. The most significant changes in the expression of 11 selected genes were detected at the developmental stage associated with completion of cardiac septation, myocardial mass expansion, and increased insulin production in the embryonic pancreas. These affected genes encode products involved in the epithelial-to-mesenchymal transition, a crucial process in heart development. Using immunohistochemistry, we detected increased hypoxia in the diabetes-exposed hearts at the critical stage of cardiac development. Correspondingly to increased hypoxia, the expression of hypoxia-inducible factor 1α (HIF1α) and vascular endothelial growth factor A was increased in the heart of diabetes-exposed embryos. Based on our results indicating the...
|
|
|
The role of mitochondrial metabolism in initiation and adaptation to hypoxic conditions.
Rohlenová, Terezie ; Novák, Petr (advisor) ; Rohlena, Jakub (referee)
We can meet pathological hypoxia in the cases of hearth attack, ischemic stroke, but also during tumor invasion, thanks to insufficient angiogenesis. The activation of HIF- 1 factor during hypoxic conditions is crucial for the cell survival. This factor modulates energetic metabolism in favor of fast progressing glycolysis (with the contribution of glutaminolysis) which provides to cell enough ATP and "building blocks", while suppressing Krebs cycle and respiration because of shortage of oxygen. The thesis studies energetic metabolism of HepG2 cells (derived from liver carcinoma) which are cultivated in the media with various energetic substrates, i. e. glucose or galactose (always together with glutamine and pyruvate) under the hypoxic conditions (5% O2). HepG2 cells use particularly oxidative metabolism for ATP and "building blocks" production under the normoxic conditions while hypoxic environment causes metabolic shift in glycemic condition. Interestingly, cells cultured in galactose (glutamine) didn't switch the energy metabolism from oxidative to aerobic glycolysis such as cells cultivated in glucose, although HIF-1 factor was stabilized. We found that enhanced activity and integrity of mitochondria, enhanced maximal capacity and reserve capacity of respiration chain correlates with...
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