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Cell death as a result of iron-induced cellular damage
Běhounek, Matěj ; Balušíková, Kamila (advisor) ; Truksa, Jaroslav (referee)
Iron is an essential trace element for almost all living organisms. Iron overload in cells and tissues, however, leads to their disruption. Most oftenly damaged are parenchymatic organs such as the liver, pancreas and heart. The aim of this thesis was to create cellular in vitro models for the investigation of effects of excess iron on hepatocytes and pancreatic beta cells and on these models to investigate cellular processes which lead to cellular damage during iron overload. We focused on examining the presence of oxidative and endoplasmic reticulum stress and the activation of apoptotic cell death. For our experiments, we used HEP-G2 cell line which represents human hepatocytes and NES2Y cell line which represents human pancreatic beta cells. To study the mechanisms of cellular damage during iron overload, we used two approaches by which we observed both acute and long-term effects of high levels of iron on damage of the tested cell lines. When studying the acute effect of excess iron on the cells, we applied high doses of iron (using 15 mM ferric citrate in medium) that led to the activation of cell death in hours. Long-term effects of iron overload were tested on cells regularly cultivated in the presence of 50 μM and 100 μM ferric citrate over a period of several months. Iron concentrations...
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Cell death as a result of iron-induced cellular damage
Běhounek, Matěj ; Balušíková, Kamila (advisor) ; Truksa, Jaroslav (referee)
Iron is an essential trace element for almost all living organisms. Iron overload in cells and tissues, however, leads to their disruption. Most oftenly damaged are parenchymatic organs such as the liver, pancreas and heart. The aim of this thesis was to create cellular in vitro models for the investigation of effects of excess iron on hepatocytes and pancreatic beta cells and on these models to investigate cellular processes which lead to cellular damage during iron overload. We focused on examining the presence of oxidative and endoplasmic reticulum stress and the activation of apoptotic cell death. For our experiments, we used HEP-G2 cell line which represents human hepatocytes and NES2Y cell line which represents human pancreatic beta cells. To study the mechanisms of cellular damage during iron overload, we used two approaches by which we observed both acute and long-term effects of high levels of iron on damage of the tested cell lines. When studying the acute effect of excess iron on the cells, we applied high doses of iron (using 15 mM ferric citrate in medium) that led to the activation of cell death in hours. Long-term effects of iron overload were tested on cells regularly cultivated in the presence of 50 μM and 100 μM ferric citrate over a period of several months. Iron concentrations...
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Effect of iron overload on the induction of apoptosis in mammalian cells
Kabíčková, Tereza ; Balušíková, Kamila (advisor) ; Klíma, Martin (referee)
Iron cations are an important metal ions required to number of essential cell functions. On the other hand, ferrous iron can be very toxic as well. When surplus iron is present in cells, it can catalyze the formation of reactive oxygen species (especially hydroxyl radicals) by Fenton reaction. Iron homeostasis is predominantly regulated by very strict mechanisms on the level of iron uptake into the body. Moreover, iron absorption, transport and storage within the body can be also regulated using complex mechanisms which differ on the level of individual cells and on the level of whole organism. Deregulation of iron homeostasis causing an iron overload and generation of reactive oxygen radicals can evoke serious cell damage leading up to apoptotic cell death. Excess iron storage and subsequent development of oxidative stress can affect lot of different tissues in the body. The organ damages such as fibrosis, cirrhosis, hepatocellular carcinoma, heart failure, loss of β cells and glucose intolerance or diabetes mellitus in patients with iron overload are very often seen. Nevertheless, the apoptosis induced by iron overload has not been well elucidated yet. There are no complex informations about the precise mechanism by which oxidative stress affects different cell types or whether there are other...
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