Reactive oxygen species induce swelling and cytochrome c release but not transmembrane depolarization in isolated rat brain mitochondria.
In this study, we have used isolated brain mitochondria to investigate the effects of superoxide anions (O2-) on mitochondrial parameters related to apoptosis, such as swelling, potential, enzymatic activity, NAD(P)H, cytochrome c release, and caspase activity.Addition of the reactive oxygen species...
| Autores: | , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2003 |
| País: | España |
| Institución: | Universidad de Castilla-La Mancha |
| Repositorio: | RUIdeRA. Repositorio Institucional de la UCLM |
| OAI Identifier: | oai:ruidera.uclm.es:10578/33366 |
| Acceso en línea: | https://hdl.handle.net/10578/33366 |
| Access Level: | acceso abierto |
| Palabra clave: | Apoptosis Brain Caspase Excitotoxicity Mitochondrion ROS |
| Sumario: | In this study, we have used isolated brain mitochondria to investigate the effects of superoxide anions (O2-) on mitochondrial parameters related to apoptosis, such as swelling, potential, enzymatic activity, NAD(P)H, cytochrome c release, and caspase activity.Addition of the reactive oxygen species (ROS) generator KO2 produced brain mitochondrial swelling, which was blocked by cyclosporin A (CSA), and which was Ca2+ independent.Calcium induced mitochondrial swelling only at high concentrations and in the presence of succinate. This correlated with the increase in O2- production detected with hydroethidine in mitochondrial preparations exposed to Ca2+ and the fact that ROS were required for Ca2+-induced mitochondrial swelling.Superoxide anions, but not Ca2+, decreased citrate synthase and dehydrogenase enzymatic activities and dropped total mitochondrial NAD(P)H levels.Calcium, but not O2-, triggered a rapid loss of mitochondrial potential. Calcium-induced ??m dissipation was inhibited by Ruthenium Red, but not by CSA.Calcium- and superoxide-induced mitochondrial swelling released cytochrome c and increased caspase activity from isolated mitochondria in a CS A-sensitive manner.In summary, superoxide potently triggers mitochondrial swelling and the release of proteins involved in activation of postmitochondrial apoptotic pathways in the absence of mitochondrial depolarization. |
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