title: Influence of metformin on mitochondrial subproteome in the brain of apoE knockout mice.
abstract: Neurodegenerative diseases are the set of progressive, age-related brain disorders, characterized by an excessive accumulation of mutant proteins in the certain regions of the brain. Such changes, collectively identified as causal factors of neurodegeneration, all impact mitochondria, imminently leading to their dysfunction. These observations predestine mitochondria as an attractive drug target for counteracting degenerative brain damage. The aim of this study was to use a differential proteomic approach to comprehensively assess the changes in mitochondrial protein expression in the brain of apoE-knockout mice (apoE(-/-)) and to investigate the influence of prolonged treatment with metformin - an indirect activator of AMP-activated protein kinase (AMPK) on the brain mitoproteome in apoE(-/-) mice. The quantitative assessment of the brain mitoproteome in apoE(-/-) revealed the changes in 10 proteins expression as compared to healthy C57BL/6J mice and 25 proteins expression in metformin-treated apoE(-/-) mice. Identified proteins mainly included apoptosis regulators, metabolic enzymes and structural proteins. In summary, our study provided proteomic characteristics suggesting the decrease of antioxidant defense and structural disturbances in the brain mitochondria of apoE(-/-) mice as compared to healthy controls. In this setting, the use of metformin changed the expression of several proteins primarily involved in metabolic processes, the regulation of apoptosis and the structural maintenance of mitochondria, what could potentially restore their native functionalities.
authors.affiliation: Chair of Pharmacology, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31 531 Krakow, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Suski
authors.affiliation: Chair of Pharmacology, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31 531 Krakow, Poland. Electronic address: mfolszan@cyf-kr.edu.pl.
authors.forename: Rafał
authors.initials: R
authors.lastname: Olszanecki
authors.affiliation: Chair of Pathomorphology, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31 531 Krakow, Poland.
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Chmura
authors.affiliation: Chair of Pharmacology, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31 531 Krakow, Poland.
authors.forename: Aneta
authors.initials: A
authors.lastname: Stachowicz
authors.affiliation: Chair of Pharmacology, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31 531 Krakow, Poland.
authors.forename: Józef
authors.initials: J
authors.lastname: Madej
authors.affiliation: Chair of Pathomorphology, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31 531 Krakow, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Okoń
authors.affiliation: Chair of Pathomorphology, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31 531 Krakow, Poland.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Adamek
authors.affiliation: Chair of Pharmacology, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31 531 Krakow, Poland.
authors.forename: Ryszard
authors.initials: R
authors.lastname: Korbut
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics*; D001921:Brain / Q000166:cytology*; D005260:Female; D008687:Metformin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D040901:Proteomics; D059467:Transcriptome / Q000187:drug effects
chemical_list: D001057:Apolipoproteins E; D008687:Metformin
keywords: AMPK; Apolipoprotein E; Brain; Metformin; Mitochondria; Proteomics