Iron is essential for cell life since it functions as an important cofactor in a multitude of vital metabolic processes and plays an essential role in cell viability. Free iron is also very toxic when present in high concentrations, thus placing this essential metal at the core of cellular injury. Pivotal role of iron in cellular homeostasis, including its latent toxicity, necessitates a tight regulation of iron metabolism. Oxygen and iron appear to play an important role in iron homeostasis and they exert this role by modulating the protein involved in iron sensing, transport, uptake and storage. These proteins include ferritin (intracellular storage), transferrin (extracellular transport), transferrin receptor and divalent metal transporter 1 (DMT-1) (uptake) and iron regulatory proteins (IRPs) (sensors of intracellular iron concentration). The interplay of iron and oxygen is most intriguing in the setting of cardiac ischemia, where hypoxia and free iron appear to interact in causing the subsequent cellular death. Hypoxia and re-establishment of tissue blood flow causes the generation of reactive oxygen species (ROS) catalysed by intracellular free iron, that converts the superoxide anion in hydroxyl radicals with deleterious effects in post-ischemic reperfused tissues. The molecular mechanisms on the basis of the regulation of iron homeostasis in the heart after hypoxia/reperfusion are still unclear. Aim of this proposed research project is to investigate the regulation of iron homeostasis in cultured cardiac cells and in in vivo model of cardiac ischemis in response to oxygen deprivation and reoxygenation. Moreover, taking in the account that the cardiac injury is tightly correlated to an increased ROS production after the hypoxia/reperfusion, it will be also studied the possible antioxidant effect of the oxalomalic acid and of several types of statins to set the bases for the development of drugs for treatment of cardiac cell on the light of an antioxidant therapy of the cardiac ischemia.
Il metabolismo del ferro in cellule cardiache: danni da ipossia e strategie protettive / Santamaria, Rita. - (2008). (Intervento presentato al convegno Il metabolismo del ferro in cellule cardiache: danni da ipossia e strategie protettive nel 01.02.2008).
Il metabolismo del ferro in cellule cardiache: danni da ipossia e strategie protettive
SANTAMARIA, RITA
2008
Abstract
Iron is essential for cell life since it functions as an important cofactor in a multitude of vital metabolic processes and plays an essential role in cell viability. Free iron is also very toxic when present in high concentrations, thus placing this essential metal at the core of cellular injury. Pivotal role of iron in cellular homeostasis, including its latent toxicity, necessitates a tight regulation of iron metabolism. Oxygen and iron appear to play an important role in iron homeostasis and they exert this role by modulating the protein involved in iron sensing, transport, uptake and storage. These proteins include ferritin (intracellular storage), transferrin (extracellular transport), transferrin receptor and divalent metal transporter 1 (DMT-1) (uptake) and iron regulatory proteins (IRPs) (sensors of intracellular iron concentration). The interplay of iron and oxygen is most intriguing in the setting of cardiac ischemia, where hypoxia and free iron appear to interact in causing the subsequent cellular death. Hypoxia and re-establishment of tissue blood flow causes the generation of reactive oxygen species (ROS) catalysed by intracellular free iron, that converts the superoxide anion in hydroxyl radicals with deleterious effects in post-ischemic reperfused tissues. The molecular mechanisms on the basis of the regulation of iron homeostasis in the heart after hypoxia/reperfusion are still unclear. Aim of this proposed research project is to investigate the regulation of iron homeostasis in cultured cardiac cells and in in vivo model of cardiac ischemis in response to oxygen deprivation and reoxygenation. Moreover, taking in the account that the cardiac injury is tightly correlated to an increased ROS production after the hypoxia/reperfusion, it will be also studied the possible antioxidant effect of the oxalomalic acid and of several types of statins to set the bases for the development of drugs for treatment of cardiac cell on the light of an antioxidant therapy of the cardiac ischemia.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
