Forschungs- & Entwicklungsinformationsdienst der Gemeinschaft - CORDIS

Novel methodologies for assessing pools of labile (toxic) iron in cells and tissues: Biological and clinical (diagnostic and therapeutic) implications

Cellular labile iron pools (LIPs) represent important physiological and pathophysiological parameters whole levels are indicative of cell iron status in health and disease. In iron overload conditions (thalassemia and hemochromatosis), elevated LIPs can compromise organ function, such as heart and endocrine glands. We developed novel fluorescent probes and microscopic methods for identifying labile iron in cells and organelles, tracing their levels in iron overload and assessing their involvement in iron toxicity.

Most importantly, we introduced the means for evaluating chelator efficacy in living cells by continuous inspection of LIP levels and have adapted those methods for high throughput screening of novel chelators in living cells and their compartments. The information gathered indicates that endocytosis represent a major route of labile plasma iron (LPI) (but also of chelator) entrance into cells such as hepatocytes, cardiomyocytes and macrophages. The discovery of such routes provides a new methodological platform for designing novel chelators as potential therapeutic agents targeted to particular cells, namely those that have high endocytic activity and accumulate relative large amount of LPI , such macrophages. The adaptation of the principle for high throughput screening of novel chelators is highly feasible and of potential commercial value.

Kontakt

Z. Ioav CABANTCHIK, (Professor)
Tel.: +972-2-6585420
Fax: +972-2-6586974
E-Mail-Adresse
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