Targeting the Lysosome: Fluorescent Iron(III) Chelators To Selectively Monitor Endosomal/Lysosomal Labile Iron Pools

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• 作者：Sarah Fakih ; Maria Podinovskaia ; Xiaole Kong ; Helen L. Collins ; Ulrich E. Schaible ; Robert C. Hider
• 刊名：Journal of Medicinal Chemistry
• 出版年：2008
• 出版时间：August 14, 2008
• 年：2008
• 卷：51
• 期：15
• 页码：4539-4552
• 全文大小：523K
• 年卷期：v.51,no.15(August 14, 2008)
• ISSN：1520-4804

文摘

Iron-sensitive fluorescent chemosensors in combination with digital fluorescence spectroscopy have led to the identification of a distinct subcellular compartmentation of intracellular redox-active “labile” iron. To investigate the distribution of labile iron, our research has been focused on the development of fluorescent iron sensors targeting the endosomal/lysosomal system. Following the recent introduction of a series of 3-hydroxypyridin-4-one (HPO) based fluorescent probes we present here two novel HPO sensors capable of accumulating and monitoring iron exclusively in endosomal/lysosomal compartments. Flow cytometric and confocal microscopy studies in murine macrophages revealed endosomal/lysosomal sequestration of the probes and high responsiveness toward alterations of vesicular labile iron concentrations. This allowed assessment of cellular iron status with high sensitivity in response to the clinically applied medications desferrioxamine, deferiprone, and deferasirox. The probes represent a powerful class of sensors for quantitative iron detection and clinical real-time monitoring of subcellular labile iron levels in health and disease.