Journal
NEUROSCIENCE LETTERS
Volume 579, Issue -, Pages 145-150Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2014.07.029
Keywords
Metformin; Phosphoproteomics; LC-MS/MS; 2DE; Brain
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Funding
- NRF - Korea Ministry of Science, ICT & Future Planning (MSIP) [NRF-2012R1A1A1012435]
- Samsung Biomedical Research Institute (SBRI) [SMX1132521]
- RCF fund [SMX1132841]
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Metformin, a potent antihyperglycemic agent is recommended as the first-line oral therapy for type 2 diabetes (T2D). Recently, metformin has been reported to be beneficial to neurodegenerative disease models. However, the putative mechanisms underlying the neuroprotective effects of metformin in disease models are unknown. Thus, we applied LC-MS/MS-based pattern analysis and two-dimensional electrophoresis (2DE)-based proteomic approach to understand the global phosphoproteomic alteration in the brain of metformin-administrated mice. Collectively, LC-MS/MS-based pattern analysis reveals that 41 phosphoproteins were upregulated and 22 phosphoproteins were downregulated in the brain of metformin-administrated mice. In addition, 5 differentially expressed phosphoproteins were identified upon metformin administration by 2DE coupled with mass spectrometry. The phosphorylation status of metabolic enzymes was decreased while that of mitochondrial proteins was increased by metformin. Interestingly, phosphorylated cc-synuclein was significantly decreased by metformin administration. Taken together, our results might provide potential pathways to understand the pharmacological effect of metformin on neuroprotection. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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