Rhein 2009 Cell Mol Neurobiol: Difference between revisions
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{{Publication | {{Publication | ||
|title=Rhein V, Baysang G, Rao S, Meier F, Bonert A, MΓΌller-Spahn F, Eckert A (2009) Amyloid-beta leads to impaired cellular respiration, energy production and mitochondrial electron chain complex activities in human neuroblastoma cells. Cell Mol Neurobiol 29: 1063-71. | |title=Rhein V, Baysang G, Rao S, Meier F, Bonert A, MΓΌller-Spahn F, Eckert A (2009) Amyloid-beta leads to impaired cellular respiration, energy production and mitochondrial electron chain complex activities in human neuroblastoma cells. Cell Mol Neurobiol 29:1063-71. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/ | |info=[http://www.ncbi.nlm.nih.gov/pubmed/19350381 PMID: 19350381] | ||
|authors=Rhein V, Baysang G, Rao S, Meier F, Bonert A, Mueller-Spahn F, Eckert A | |authors=Rhein V, Baysang G, Rao S, Meier F, Bonert A, Mueller-Spahn F, Eckert A | ||
|year=2009 | |year=2009 | ||
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|abstract=Evidence suggests that amyloid-beta (AΞ²) protein is a key factor in the pathogenesis of Alzheimerβs disease (AD) and it has been recently proposed that mitochondria are involved in the biochemical pathway by which AΞ² can lead to neuronal dysfunction. Here we investigated the specific effects of AΞ² on mitochondrial function under physiological conditions. Mitochondrial respiratory functions and energy metabolism were analyzed in control and in human wild-type amyloid precursor protein (APP) stably transfected human neuroblastoma cells (SH-SY5Y). Mitochondrial respiratory capacity of mitochondrial electron transport chain (ETC) in vital cells was measured with a high-resolution respirometry system (Oxygraph-2k). In addition, we determined the individual activities of mitochondrial complexes IβIV that compose ETC and ATP cellular levels. While the activities of complexes I and II did not change between cell types, complex IV activity was significantly reduced in APP cells. In contrast, activity of complex III was significantly enhanced in APP cells, as compensatory response in order to balance the defect of complex IV. However, this compensatory mechanism could not prevent the strong impairment of total respiration in vital APP cells. As a result, the respiratory control ratio (state3/state4) together with ATP production decreased in the APP cells in comparison with the control cells. Chronic exposure to soluble AΞ² protein may result in an impairment of energy homeostasis due to a decreased respiratory capacity of mitochondrial electron transport chain which, in turn, may accelerate neurons demise. | |abstract=Evidence suggests that amyloid-beta (AΞ²) protein is a key factor in the pathogenesis of Alzheimerβs disease (AD) and it has been recently proposed that mitochondria are involved in the biochemical pathway by which AΞ² can lead to neuronal dysfunction. Here we investigated the specific effects of AΞ² on mitochondrial function under physiological conditions. Mitochondrial respiratory functions and energy metabolism were analyzed in control and in human wild-type amyloid precursor protein (APP) stably transfected human neuroblastoma cells (SH-SY5Y). Mitochondrial respiratory capacity of mitochondrial electron transport chain (ETC) in vital cells was measured with a high-resolution respirometry system (Oxygraph-2k). In addition, we determined the individual activities of mitochondrial complexes IβIV that compose ETC and ATP cellular levels. While the activities of complexes I and II did not change between cell types, complex IV activity was significantly reduced in APP cells. In contrast, activity of complex III was significantly enhanced in APP cells, as compensatory response in order to balance the defect of complex IV. However, this compensatory mechanism could not prevent the strong impairment of total respiration in vital APP cells. As a result, the respiratory control ratio (state3/state4) together with ATP production decreased in the APP cells in comparison with the control cells. Chronic exposure to soluble AΞ² protein may result in an impairment of energy homeostasis due to a decreased respiratory capacity of mitochondrial electron transport chain which, in turn, may accelerate neurons demise. | ||
|keywords=Mitochondria,Β Amyloid-beta, SH-SY5Y cells, Respiration,Β Electron chain,Β Energy, ATP , Oxygen consumption | |keywords=Mitochondria,Β Amyloid-beta, SH-SY5Y cells, Respiration,Β Electron chain,Β Energy, ATP , Oxygen consumption | ||
|mipnetlab= | |mipnetlab=CH Basel Eckert A | ||
|discipline=Biomedicine | |discipline=Biomedicine | ||
}} | }} | ||
{{Labeling | {{Labeling | ||
|area=Respiration, mt-Medicine | |||
|diseases=Alzheimer's, Neurodegenerative | |||
|organism=Human | |||
|tissues=Nervous system, Neuroblastoma | |||
|preparations=Permeabilized cells | |||
|enzymes=Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase | |||
|couplingstates=LEAK | |||
|pathways=N, S, NS, ROX | |||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
|discipline=Biomedicine | |discipline=Biomedicine | ||
}} | }} | ||
Latest revision as of 16:14, 9 November 2016
| Rhein V, Baysang G, Rao S, Meier F, Bonert A, MΓΌller-Spahn F, Eckert A (2009) Amyloid-beta leads to impaired cellular respiration, energy production and mitochondrial electron chain complex activities in human neuroblastoma cells. Cell Mol Neurobiol 29:1063-71. |
Rhein V, Baysang G, Rao S, Meier F, Bonert A, Mueller-Spahn F, Eckert A (2009) Cell Mol Neurobiol
Abstract: Evidence suggests that amyloid-beta (AΞ²) protein is a key factor in the pathogenesis of Alzheimerβs disease (AD) and it has been recently proposed that mitochondria are involved in the biochemical pathway by which AΞ² can lead to neuronal dysfunction. Here we investigated the specific effects of AΞ² on mitochondrial function under physiological conditions. Mitochondrial respiratory functions and energy metabolism were analyzed in control and in human wild-type amyloid precursor protein (APP) stably transfected human neuroblastoma cells (SH-SY5Y). Mitochondrial respiratory capacity of mitochondrial electron transport chain (ETC) in vital cells was measured with a high-resolution respirometry system (Oxygraph-2k). In addition, we determined the individual activities of mitochondrial complexes IβIV that compose ETC and ATP cellular levels. While the activities of complexes I and II did not change between cell types, complex IV activity was significantly reduced in APP cells. In contrast, activity of complex III was significantly enhanced in APP cells, as compensatory response in order to balance the defect of complex IV. However, this compensatory mechanism could not prevent the strong impairment of total respiration in vital APP cells. As a result, the respiratory control ratio (state3/state4) together with ATP production decreased in the APP cells in comparison with the control cells. Chronic exposure to soluble AΞ² protein may result in an impairment of energy homeostasis due to a decreased respiratory capacity of mitochondrial electron transport chain which, in turn, may accelerate neurons demise. β’ Keywords: Mitochondria, Amyloid-beta, SH-SY5Y cells, Respiration, Electron chain, Energy, ATP, Oxygen consumption
β’ O2k-Network Lab: CH Basel Eckert A
Labels: MiParea: Respiration, mt-Medicine
Pathology: Alzheimer's, Neurodegenerative
Organism: Human Tissue;cell: Nervous system, Neuroblastoma Preparation: Permeabilized cells Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase
Coupling state: LEAK Pathway: N, S, NS, ROX HRR: Oxygraph-2k
