Metallothionein protects against oxidative stress-induced lysosomal destabilization
2006 (English)In: Biochemical Journal, ISSN 0264-6021, Vol. 394, no 1, 275-283 p.Article in journal (Refereed) Published
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.
apoptosis, autophagocytosis, lysosome, metallothionein, oxidative stress, redox-active iron
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-32600DOI: 10.1042/BJ20051143Local ID: 18515OAI: oai:DiVA.org:liu-32600DiVA: diva2:253423