Difference between revisions of "Lim 2010 Proteomics"
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{{Publication | {{Publication | ||
|title=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- | |title=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. | ||
|authors=Lim YA, Rhein V, Baysang G, Meier F, Poljak A, Raftery MJ, Guilhaus M, Ittner LM, Eckert A, Goetz J | |info=[http://www.ncbi.nlm.nih.gov/pubmed/20186753 PMID: 20186753 ] | ||
|authors=Lim YA, Rhein V, Baysang G, Meier F, Poljak A, Raftery MJ, Guilhaus M, Ittner LM, Eckert A, Goetz J | |||
|year=2010 | |year=2010 | ||
|journal=Proteomics | |journal=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. | |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) | |keywords=Alzheimer's disease (AD), Type 2 diabetes mellitus (T2DM), Human amylin (HA), Complex IV, Complex I, ROS, Aging | ||
| | |mipnetlab=CH Basel Eckert A | ||
|discipline=Environmental Physiology; Toxicology, Pharmacology; Biotechnology | |||
|articletype=Protocol; Manual | |||
}} | }} | ||
{{Labeling | {{Labeling | ||
|area=Respiration, Pharmacology;toxicology | |||
|organism=Human | |||
|tissues=Nervous system | |||
|preparations=Intact cells | |||
|enzymes=Complex I, Complex IV;cytochrome c oxidase | |||
|injuries=Oxidative stress;RONS | |||
|diseases=Aging;senescence, Alzheimer's, Diabetes, Neurodegenerative | |||
|topics=Redox state | |||
|couplingstates=OXPHOS | |||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
| | |discipline=Environmental Physiology; Toxicology, Pharmacology; Biotechnology | ||
|articletype=Protocol; Manual | |||
| | |||
}} | }} | ||
Latest revision as of 16:41, 17 March 2015
| 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. • 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
