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.
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Research Article|
January 27 2006
Metallothionein protects against oxidative stress-induced lysosomal destabilization
Sarah K. Baird;
Sarah K. Baird
1
*Division of Pharmacology, Faculty of Health Sciences, Linköping University, S-58185 Linköping, Sweden
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Tino Kurz;
Tino Kurz
1
*Division of Pharmacology, Faculty of Health Sciences, Linköping University, S-58185 Linköping, Sweden
†Henry Wellcome Laboratory for Biogerontology Research, School of Clinical Medical Sciences-Gerontology, University of Newcastle upon Tyne, Newcastle upon Tyne NE4 6BE, U.K.
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Ulf T. Brunk
Ulf T. Brunk
2
*Division of Pharmacology, Faculty of Health Sciences, Linköping University, S-58185 Linköping, Sweden
2To whom correspondence should be addressed (email Ulf.Brunk@imv.liu.se).
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Publisher: Portland Press Ltd
Received:
July 15 2005
Revision Received:
October 11 2005
Accepted:
October 19 2005
Accepted Manuscript online:
October 19 2005
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2006
Biochem J (2006) 394 (1): 275–283.
Article history
Received:
July 15 2005
Revision Received:
October 11 2005
Accepted:
October 19 2005
Accepted Manuscript online:
October 19 2005
Citation
Sarah K. Baird, Tino Kurz, Ulf T. Brunk; Metallothionein protects against oxidative stress-induced lysosomal destabilization. Biochem J 15 February 2006; 394 (1): 275–283. doi: https://doi.org/10.1042/BJ20051143
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