Difference between revisions of "Lim 2010 Proteomics"
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{{Labeling | {{Labeling | ||
|area=Respiration, Pharmacology; toxicology | |||
|organism=Human | |organism=Human | ||
|tissues=Nervous system | |tissues=Nervous system | ||
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|enzymes=Complex I, Complex IV; Cytochrome c Oxidase | |enzymes=Complex I, Complex IV; Cytochrome c Oxidase | ||
|injuries=RONS; Oxidative Stress | |injuries=RONS; Oxidative Stress | ||
|diseases=Aging; senescence, Alzheimer's, Diabetes, Neurodegenerative | |diseases=Aging; senescence, Alzheimer's, Diabetes 2, Neurodegenerative | ||
|topics=Redox state | |topics=Redox state | ||
|couplingstates=OXPHOS | |couplingstates=OXPHOS | ||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k |
Revision as of 13:05, 9 August 2013
Lim YA, Rhein V, Baysang G, Meier F, Poljak A, Raftery MJ, Guilhaus M, Ittner LM, Eckert A, Goetz J (2010) Abeta and human amylin share a common toxicity pathway via mitochondrial dysfunction. Proteomics 10: 1621-1633. |
Lim YA, Rhein V, Baysang G, Meier F, Poljak A, Raftery MJ, Guilhaus M, Ittner LM, Eckert A, Goetz J (2010) Proteomics
Abstract: Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) are leading causes of morbidity and mortality in the elderly. Both diseases are characterized by amyloid deposition in target tissues: aggregation of amylin in T2DM is associated with loss of insulin-secreting beta-cells, while amyloid beta (A beta) aggregation in AD brain is associated with neuronal loss. Here, we used quantitative iTRAQ proteomics as a discovery tool to show that both A beta and human amylin (HA) deregulate identical proteins, a quarter of which are mitochondrial, supporting the notion that mitochondrial dysfunction is a common target in these two amyloidoses. A functional validation revealed that mitochondrial complex IV activity was significantly reduced after treatment with either HA or A beta, as was mitochondrial respiration. In comparison, complex I activity was reduced only after treatment with HA. A beta and HA, but not the non-amyloidogenic rat amylin, induced significant increases in the generation of ROS. Co-incubation of HA and A beta did not produce an augmented effect in ROS production, again suggesting common toxicity mechanisms. In conclusion, our data suggest that A beta and HA both exert toxicity, at least in part, via mitochondrial dysfunction, thus restoring their function may be beneficial for both AD and T2DM. β’ Keywords: Alzheimer's disease (AD), type 2 diabetes mellitus (T2DM), human amylin (HA), complex IV, complex I, ROS, aging
β’ O2k-Network Lab: CH_Basel_Eckert A
Labels: MiParea: Respiration, Pharmacology; toxicology"Pharmacology; toxicology" is not in the list (Respiration, Instruments;methods, mt-Biogenesis;mt-density, mt-Structure;fission;fusion, mt-Membrane, mtDNA;mt-genetics, nDNA;cell genetics, Genetic knockout;overexpression, Comparative MiP;environmental MiP, Gender, ...) of allowed values for the "MiP area" property.
Pathology: Aging; senescence"Aging; senescence" is not in the list (Aging;senescence, Alzheimer's, Autism, Cancer, Cardiovascular, COPD, Diabetes, Inherited, Infectious, Myopathy, ...) of allowed values for the "Diseases" property., Alzheimer's, Diabetes 2"Diabetes 2" is not in the list (Aging;senescence, Alzheimer's, Autism, Cancer, Cardiovascular, COPD, Diabetes, Inherited, Infectious, Myopathy, ...) of allowed values for the "Diseases" property., Neurodegenerative
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.
Organism: Human
Tissue;cell: Nervous system
Preparation: Intact cells
Enzyme: Complex I, Complex IV; Cytochrome c Oxidase"Complex IV; Cytochrome c Oxidase" 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: Redox state
Coupling state: OXPHOS
HRR: Oxygraph-2k