Lim 2010 Proteomics
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 10:1621-33. |
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
Pathology: Aging;senescence, Alzheimer's, Diabetes, Neurodegenerative
Stress:Oxidative stress;RONS
Organism: Human
Tissue;cell: Nervous system
Preparation: Intact cells
Enzyme: Complex I, Complex IV;cytochrome c oxidase
Regulation: Redox state
Coupling state: OXPHOS
HRR: Oxygraph-2k