Effect of reactive oxygen species on lysosomal membrane integrity View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1993-12

AUTHORS

Johann M. Zdolsek, Iréne Svensson

ABSTRACT

Using a lysosome-enriched “light mitochondrial” fraction of a rat liver homogenate, the effects of the reactive oxygen species hydrogen peroxide, superoxide and hydroxyl radicals were determined. Alterations in the intralysosomal pH and the release of a lysosomal marker enzyme, N-acetyl-glucosaminidase, were used as indicators of changes in the lysosomal membrane integrity. Lipid peroxidation of the fraction was assayed by TBARS measurement. Neither superoxide radicals, generated by hypoxanthine/xanthine oxidase, nor a bolus dose of hydrogen peroxide (0.5–1.5 mM) induced any lysosomal damage. If, however, Fe(III)ADP was included in the superoxide radical-generating system, lysosomal membrane damage was detected, both as an increase in lysosomal pH and as a release of N-acetyl-glucosaminidase, but only after a lag phase of about 7 min. Lipid peroxidation, on the other hand, proceeded gradually. Lysosomes treated with hydrogen peroxide displayed similar dose-dependent alterations, albeit only if both Fe(III)ADP and the reducing amino acid cysteine were added. In the latter system, however, alterations of the lysosomal membrane stability occurred more rapidly, showing a lag phase of only 2 min. Lipid peroxidation, which proceeded faster and displayed no lag phase, levelled out within 10 min. The results indicate that neither superoxide radicals nor hydrogen peroxide are by themselves damaging to lysosomes. Available catalytically active iron in Fe(II) form, however, allows reactions yielding powerful oxidative species—probably hydroxyl radicals formed via Fenton reactions—to take place inducing peroxidation of the lysosomal membranes resulting in dissipation of the proton-gradient and leakage of their enzyme contents. More... »

PAGES

401

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/bf02915141

DOI

http://dx.doi.org/10.1007/bf02915141

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https://app.dimensions.ai/details/publication/pub.1017823542


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