title: The biguanide metformin alters phosphoproteomic profiling in mouse brain.
abstract: 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 α-synuclein was significantly decreased by metformin administration. Taken together, our results might provide potential pathways to understand the pharmacological effect of metformin on neuroprotection.
authors: Division of Pharmacology, Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.
authors: Rin
authors: R
authors: Khang
authors: Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea; Mass Spectrometry, Research Core Facility, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.
authors: ChiHu
authors: C
authors: Park
authors: Division of Pharmacology, Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea. Electronic address: jshin24@skku.edu.
authors: Joo-Ho
authors: JH
authors: Shin
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects / Q000235:genetics; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D030541:Databases, Genetic; D020869:Gene Expression Profiling; D056726:Genetic Association Studies; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D008687:Metformin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics*; D040901:Proteomics
chemical_list: D007004:Hypoglycemic Agents; D010750:Phosphoproteins; D008687:Metformin; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: 2DE; Brain; LC–MS/MS; Metformin; Phosphoproteomics