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Metallothionein protects against oxidative stress-induced lysosomal destabilization
Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
2006 (English)In: Biochemical Journal, ISSN 0264-6021, Vol. 394, no 1, 275-283 p.Article in journal (Refereed) Published
Abstract [en]

The introduction of apo-ferritin or the iron chelator DFO (desferrioxamine) conjugated to starch into the lysosomal compartment protects cells against oxidative stress, lysosomal rupture and ensuing apoptosis/necrosis by binding intralysosomal redox-active iron, thus preventing Fenton-type reactions and ensuing peroxidation of lysosomal membranes. Because up-regulation of MTs (metallothioneins) also generates enhanced cellular resistance to oxidative stress, including X-irradiation, and MTs were found to be capable of iron binding in an acidic and reducing lysosomal-like environment, we propose that these proteins might similarly stabilize lysosomes following autophagocytotic delivery to the lysosomal compartment. Here, we report that Zn-mediated MT up-regulation, assayed by Western blotting and immunocytochemistry, results in lysosomal stabilization and decreased apoptosis following oxidative stress, similar to the protection afforded by fluid-phase endocytosis of apo-ferritin or DFO. In contrast, the endocytotic uptake of an iron phosphate complex destabilized lysosomes against oxidative stress, but this was suppressed in cells with up-regulated MT. It is suggested that the resistance against oxidative stress, known to occur in MT-rich cells, may be a consequence of autophagic turnover of MT, resulting in reduced iron-catalysed intralysosomal peroxidative reactions. © 2006 Biochemical Society.

Place, publisher, year, edition, pages
2006. Vol. 394, no 1, 275-283 p.
Keyword [en]
apoptosis, autophagocytosis, lysosome, metallothionein, oxidative stress, redox-active iron
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-32600DOI: 10.1042/BJ20051143Local ID: 18515OAI: diva2:253423
Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2011-01-11

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