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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 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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