Oxidant-induced apoptosis: a consequence of lethal lysosomal leak?
| Autor: | Iréne Svensson, Ulf T. Brunk, H. B. Hellquist |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
0301 basic medicine
Cathepsin Necrosis 030102 biochemistry & molecular biology Physiology Biochemistry (medical) Clinical Biochemistry Acridine orange Cell Biology Oxidative phosphorylation 030204 cardiovascular system & hematology medicine.disease_cause Biochemistry Cell biology 03 medical and health sciences Cytosol chemistry.chemical_compound 0302 clinical medicine chemistry Apoptosis medicine medicine.symptom Hydrogen peroxide Oxidative stress |
| Zdroj: | Redox Report. 3:65-70 |
| ISSN: | 1743-2928 1351-0002 |
| Popis: | When macrophage-like J-774 cells are subjected to limited oxidative stress, such as exposure to hydrogen peroxide in a moderate bolus dose, some of their lysosomes rupture-as here assayed by the acridine orange relocalization test-secondary to intralysosomal, iron-catalysed, oxidative reactions. The resultant leakage into the cytosol of hydrolytic enzymes, such as cathepsin-D (as shown here), may initiate a slow degradation/fragmentation process of an apoptotic type within cells still having intact plasma membranes. In contrast, severe oxidative stress also results in extensive lysosomal rupture but leads to necrosis. The chelation of (normally occurring) intralysosomal low-molecular weight iron, by endocytotic uptake of desferrioxamine, largely prevents oxidative stress-induced apoptosis whereas lysosomal iron-loading, by endocytotic uptake of complexed ferric iron, considerably enhances the process. We conclude that oxidant-mediated and iron-catalysed lysosomal rupture leads to decompartmentalization of lysosomal enzymes which in turn may initiate and promote the apoptotic process. |
| Databáze: | OpenAIRE |
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