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Metallothionein pro...
Metallothionein protects against oxidative stress-induced lysosomal destabilization
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Baird, Sarah K (författare)
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- Kurz, Tino, 1974- (författare)
- Linköpings universitet,Hälsouniversitetet,Farmakologi
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- Brunk, Ulf, 1937- (författare)
- Linköpings universitet,Hälsouniversitetet,Farmakologi
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(creator_code:org_t)
- 2006
- 2006
- Engelska.
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Ingår i: Biochemical Journal. - 0264-6021 .- 1470-8728. ; 394:1, s. 275-283
- Relaterad länk:
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https://urn.kb.se/re...
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visa fler...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Nyckelord
- apoptosis
- autophagocytosis
- lysosome
- metallothionein
- oxidative stress
- redox-active iron
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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