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Metallothionein protects against oxidative stress-induced lysosomal destabilization
Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Farmakologi.
Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Farmakologi.
2006 (Engelska)Ingår i: Biochemical Journal, ISSN 0264-6021, E-ISSN 1470-8728, Vol. 394, nr 1, s. 275-283Artikel i tidskrift (Refereegranskat) 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.

Ort, förlag, år, upplaga, sidor
2006. Vol. 394, nr 1, s. 275-283
Nyckelord [en]
apoptosis, autophagocytosis, lysosome, metallothionein, oxidative stress, redox-active iron
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
URN: urn:nbn:se:liu:diva-32600DOI: 10.1042/BJ20051143Lokalt ID: 18515OAI: oai:DiVA.org:liu-32600DiVA, id: diva2:253423
Tillgänglig från: 2009-10-09 Skapad: 2009-10-09 Senast uppdaterad: 2017-12-13

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Kurz, TinoBrunk, Ulf

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