title: The effects of the DNA methyltranfserases inhibitor 5-Azacitidine on ageing, oxidative stress and DNA methylation of adipose derived stem cells.
abstract: Human adipose tissue is a great source of adult mesenchymal stem cells (MSCs) which are recognized from their ability to self-renew and differentiation into multiple lineages. MSCs have promised a vast therapeutic potential in treatment many diseases including tissue injury and immune disorders. However, their regenerative potential profoundly depends on patients' age. Age-related deterioration of MSC is associated with cellular senescence mainly caused by increased DNA methylation status, accumulation of oxidative stress factors and mitochondria dysfunction. We found that DNA methyltransferase (DNMT) inhibitor i.e. 5-Azacytidine (5-AZA) reversed the aged phenotype of MSCs. Proliferation rate of cells cultured with 5-AZA was increased while the accumulation of oxidative stress factors and DNA methylation status were decreased. Simultaneously the mRNA levels of TET proteins involved in demethylation process were elevated in those cells. Moreover, cells treated with 5-AZA displayed reduced reactive oxygen species (ROS) accumulation, ameliorated superoxide dismutase activity and increased BCL-2/BAX ratio in comparison to control group. Our results indicates that, treating MSCs with 5-AZA can be justified therapeutic intervention, that can slow-down and even reverse aged- related degenerative changes in those cells.
authors.affiliation: Faculty of Biology, University of Environmental and Life Sciences, Wrocław, Poland.|Wroclaw Research Centre EIT+, Wrocław, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kornicka
authors.affiliation: Faculty of Biology, University of Environmental and Life Sciences, Wrocław, Poland.|Wroclaw Research Centre EIT+, Wrocław, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Marycz
authors.affiliation: Faculty of Veterinary Medicine, University of Environmental and Life Sciences, Wrocław, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Marędziak
authors.affiliation: Department of Anatomy, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Krzysztof A
authors.initials: KA
authors.lastname: Tomaszewski
authors.affiliation: Department of Surgery, Faculty of Veterinary Medicine, University of Environmental and Life Sciences Wroclaw, Wroclaw, Poland.
authors.forename: Jakub
authors.initials: J
authors.lastname: Nicpoń
mesh_terms: D000273:Adipose Tissue / Q000473:pathology*; D000368:Aged; D000954:Antigens, Surface / Q000378:metabolism; D001374:Azacitidine / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects*; D002999:Clone Cells; D003470:Culture Media / Q000494:pharmacology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D039902:Multipotent Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000954:Antigens, Surface; D003470:Culture Media; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004791:Enzyme Inhibitors; D019394:Ki-67 Antigen; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D004248:DNA (Cytosine-5-)-Methyltransferases; D001374:Azacitidine
keywords: 5-Azacitidine; ageing; mesenchymal stem cells; methylation; oxidative stress