Iglesias-Gonzalez 2012 Neurochem Res
| Iglesias-Gonzalez J, Sanchez-Iglesias S, Mendez-Alvarez E, Rose S, Hikima A, Jenner P, Soto-Otero R (2012) Differential toxicity of 6-hydroxydopamine in SH-SY5Y human neuroblastoma cells and rat brain mitochondria: protective role of catalase and superoxide dismutase. Neurochem Res 37: 2150-2160. |
Iglesias-Gonzalez J, Sanchez-Iglesias S, Mendez-Alvarez E, Rose S, Hikima A, Jenner P, Soto-Otero R (2012) Neurochem Res
Abstract: Oxidative stress and mitochondrial dysfunction are two pathophysiological factors often associated with the neurodegenerative process involved in Parkinson's disease (PD). Although, 6-hydroxydopamine (6-OHDA) is able to cause dopaminergic neurodegeneration in experimental models of PD by an oxidative stress-mediated process, the underlying molecular mechanism remains unclear. It has been established that some antioxidant enzymes such as catalase (CAT) and superoxide dismutase (SOD) are often altered in PD, which suggests a potential role of these enzymes in the onset and/or development of this multifactorial syndrome. In this study we have used high-resolution respirometry to evaluate the effect of 6-OHDA on mitochondrial respiration of isolated rat brain mitochondria and the lactate dehydrogenase cytotoxicity assay to assess the percentage of cell death induced by 6-OHDA in human neuroblastoma cell line SH-SY5Y. Our results show that 6-OHDA affects mitochondrial respiration by causing a reduction in both respiratory control ratio (IC(50) = 200 ยฑ 15 nM) and state 3 respiration (IC(50) = 192 ยฑ 17 nM), with no significant effects on state 4(o). An inhibition in the activity of both complex I and V was also observed. 6-OHDA also caused cellular death in human neuroblastoma SH-SY5Y cells (IC(50) = 100 ยฑ 9 ฮผM). Both SOD and CAT have been shown to protect against the toxic effects caused by 6-OHDA on mitochondrial respiration. However, whereas SOD protects against 6-OHDA-induced cellular death, CAT enhances its cytotoxicity. The here reported data suggest that both superoxide anion and hydroperoxyl radical could account for 6-OHDA toxicity. Furthermore, factors reducing the rate of 6-OHDA autoxidation to its p-quinone appear to enhance its cytotoxicity. โข Keywords: Parkinson's disease, 6-hydroxydopamine (6-OHDA)
โข O2k-Network Lab: ES Santiago De Compostela Mendez-Alvarez E
Labels:
Stress:RONS; Oxidative Stress"RONS; Oxidative Stress" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property., Mitochondrial Disease; Degenerative Disease and Defect"Mitochondrial Disease; Degenerative Disease and Defect" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property. Organism: Rat Tissue;cell: Neurons; Brain"Neurons; Brain" is not in the list (Heart, Skeletal muscle, Nervous system, Liver, Kidney, Lung;gill, Islet cell;pancreas;thymus, Endothelial;epithelial;mesothelial cell, Blood cells, Fat, ...) of allowed values for the "Tissue and cell" property. Preparation: Isolated Mitochondria"Isolated Mitochondria" is not in the list (Intact organism, Intact organ, Permeabilized cells, Permeabilized tissue, Homogenate, Isolated mitochondria, SMP, Chloroplasts, Enzyme, Oxidase;biochemical oxidation, ...) of allowed values for the "Preparation" property. Enzyme: TCA Cycle and Matrix Dehydrogenases"TCA Cycle and Matrix Dehydrogenases" is not in the list (Adenine nucleotide translocase, Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase, Inner mt-membrane transporter, Marker enzyme, Supercomplex, TCA cycle and matrix dehydrogenases, ...) of allowed values for the "Enzyme" property., Complex V; ATP Synthase"Complex V; ATP Synthase" is not in the list (Adenine nucleotide translocase, Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase, Inner mt-membrane transporter, Marker enzyme, Supercomplex, TCA cycle and matrix dehydrogenases, ...) of allowed values for the "Enzyme" property. Regulation: Flux Control; Threshold; Excess Capacity"Flux Control; Threshold; Excess Capacity" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property. Coupling state: LEAK, OXPHOS, ETS"ETS" is not in the list (LEAK, ROUTINE, OXPHOS, ET) of allowed values for the "Coupling states" property.
HRR: Oxygraph-2k
