TAILIEUCHUNG - Báo cáo khoa học: Intralysosomal iron chelation protects against oxidative stress-induced cellular damage

Oxidant-induced cell damage may be initiated by peroxidative injury to lysosomal membranes, catalyzed by intralysosomal low mass iron that appears to comprise a major part of cellular redox-active iron. Resulting relocation of lytic enzymes and low mass iron would result in secondary harm to various cellular constituents. | iFEBS Journal Intralysosomal iron chelation protects against oxidative stress-induced cellular damage Tino Kurz1 Bertil Gustafsson2 and Ulf T. Brunk1 1 Division of Pharmacology Faculty of Health Sciences Linkoping University Sweden 2 Department of Pathology and Cytology University Hospital Linkoping Sweden Keywords cell death lysosomes mitochondria redoxactive iron salicylaldehyde isonicotinoyl hydrazone Correspondence U. T. Brunk Department of Pharmacology University Hospital SE-581 85 Linkoping Sweden Fax 46 13 149106 Tel 46 13 221515 E-mail Received 1 March 2006 revised 28 April 2006 accepted 15 May 2006 doi Oxidant-induced cell damage may be initiated by peroxidative injury to lysosomal membranes catalyzed by intralysosomal low mass iron that appears to comprise a major part of cellular redox-active iron. Resulting relocation of lytic enzymes and low mass iron would result in secondary harm to various cellular constituents. In an effort to further clarify this still controversial issue we tested the protective effects of two potent iron chelators - the hydrophilic desferrioxamine dfo and the lipophilic salicylaldehyde isonicotinoyl hydrazone sih using cultured lysosome-rich macrophage-like J774 cells as targets. dfo slowly enters cells via endocytosis while the lipophilic sih rapidly distributes throughout the cell. Following dfo treatment long-term survival of cells cannot be investigated because dfo by itself by remaining inside the lysosomal compartment induces apoptosis that probably is due to iron starvation while sih has no lasting toxic effects if the exposure time is limited. Following preincubation with 1 mM dfo for 3 h or 10 pM sih for a few minutes both agents provided strong protection against an ensuing LD50 oxidant challenge by preventing lysosomal rupture ensuing loss of mitochondrial membrane potential and apoptotic necrotic cell death. It appears that once significant lysosomal rupture has .

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