Lim 2010 Proteomics

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Publications in the MiPMap
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.

» PMID: 20186753

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.

Keywords: Alzheimer's disease (AD), Type 2 diabetes mellitus (T2DM), Human amylin (HA), Complex IV, Complex I, ROS, Aging

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