Showing papers by "Joaquín Jordán published in 2005"
TL;DR: In mitochondria isolated suspensions, minocycline failed to block superoxide-induced swelling but was effective in blocking mitochondrial swelling induced by calcium, which might be mediated through dissipation of mitochondrial transmembrane potential and blockade of mitochondrial calcium uptake.
64 citations
TL;DR: Data suggest that malonate causes a rapid mitochondrial potential collapse and reactive oxygen species production that overwhelms mitochondrial antioxidant capacity and leads to mitochondrial swelling, and further permeability transition pore opening and the subsequent release of proapoptotic factors such as Cyt c could be, at least in part, responsible formalonate‐induced toxicity.
Abstract: 1. Herein we study the effects of the mitochondrial complex II inhibitor malonate on its primary target, the mitochondrion. 2. Malonate induces mitochondrial potential collapse, mitochondrial swelling, cytochrome c (Cyt c) release and depletes glutathione (GSH) and nicotinamide adenine dinucleotide coenzyme (NAD(P)H) stores in brain-isolated mitochondria. 3. Although, mitochondrial potential collapse was almost immediate after malonate addition, mitochondrial swelling was not evident before 15 min of drug presence. This latter effect was blocked by cyclosporin A (CSA), Ruthenium Red (RR), magnesium, catalase, GSH and vitamin E. 4. Malonate added to SH-SY5Y cell cultures produced a marked loss of cell viability together with the release of Cyt c and depletion of GSH and NAD(P)H concentrations. All these effects were not apparent in SH-SY5Y cells overexpressing Bcl-xL. 5. When GSH concentrations were lowered with buthionine sulphoximine, cytoprotection afforded by Bcl-xL overexpression was not evident anymore. 6. Taken together, all these data suggest that malonate causes a rapid mitochondrial potential collapse and reactive oxygen species production that overwhelms mitochondrial antioxidant capacity and leads to mitochondrial swelling. Further permeability transition pore opening and the subsequent release of proapoptotic factors such as Cyt c could therefore be, at least in part, responsible for malonate-induced toxicity.
64 citations
TL;DR: It is shown that, in rat cerebellar granular cells, the succinate dehydrogenase inhibitor malonate induces cell death in a concentration-dependent manner, and suggests that the minocycline protection observed in several neurodegenerative disease models is selective, since it is absent from cultured Cerebellargranular cells challenged with malonates.
33 citations
TL;DR: It is reported that minocycline affords no protection against the neurotoxicity caused by malonate or N-methyl-d-aspartate (NMDA), and the putative NMDA receptor antagonist, MK-801, blocked the toxicity caused by both toxins indicating that, although by different mechanisms, excitotoxicity is mediating neuronal death.
22 citations
TL;DR: The data demonstrate the importance of p53 and the downstream activation of the mitochondrial apoptosis pathway in depolarization-induced apoptosis and protective effects of antioxidants in this system.
19 citations