Methylmercury and H2O2 provoke lysosomal damage in human astrocytoma D384 cells followed by apoptosisShow others and affiliations
2001 (English)In: Free Radical Biology & Medicine, ISSN 0891-5849, E-ISSN 1873-4596, Vol. 30, no 12, p. 1347-1356Article in journal (Refereed) Published
Abstract [en]
Methylmercury (MeHg) is a neurotoxic agent acting via diverse mechanisms, including oxidative stress. MeHg also induces astrocytic dysfunction, which can contribute to neuronal damage. The cellular effects of MeHg were investigated in human astrocytoma D384 cells, with special reference to the induction of oxidative-stress-related events. Lysosomal rupture was detected after short MeHg-exposure (1 μM, 1 h) in cells maintaining plasma membrane integrity. Disruption of lysosomes was also observed after hydrogen peroxide (H2O2) exposure (100 μM, 1 h), supporting the hypothesis that lysosomal membranes represent a possible target of agents causing oxidative stress. The lysosomal alterations induced by MeHg and H2O2 preceded a decrease of the mitochondrial potential. At later time points, both toxic agents caused the appearance of cells with apoptotic morphology, chromatin condensation, and regular DNA fragmentation. However, MeHg and H2O2 stimulated divergent pathways, with caspases being activated only by H2O2. The caspase inhibitor z-VAD-fmk did not prevent DNA fragmentation induced by H2O2, suggesting that the formation of high-molecular-weight DNA fragments was caspase independent with both MeHg and H2O2. The data point to the possibility that lysosomal hydrolytic enzymes act as executor factors in D384 cell death induced by oxidative stress.
Place, publisher, year, edition, pages
Linköping: Elsevier, 2001. Vol. 30, no 12, p. 1347-1356
Keywords [en]
Methylmercury, Hydrogen peroxide, Lysosomes, Mitochondrial potential, Caspases, DNA fragmentation, Free radicals
National Category
Medical Biotechnology
Identifiers
URN: urn:nbn:se:liu:diva-157130DOI: 10.1016/S0891-5849(01)00526-3PubMedID: 11390179Scopus ID: 2-s2.0-0035877037OAI: oai:DiVA.org:liu-157130DiVA, id: diva2:1318856
2019-05-282019-05-282019-06-05Bibliographically approved