title: Cytosolic Extract of Human Adipose Stem Cells Reverses the Amyloid Beta-Induced Mitochondrial Apoptosis via P53/Foxo3a Pathway.
abstract: Human adipose stem cells (hASC) have therapeutic potential for the treatment of neurodegenerative disorders. Mitochondrial dysfunction is frequently observed in most neurodegenerative disorders, including Alzheimer's disease. We explored the therapeutic potential of hASC cytosolic extracts to attenuate neuronal death induced by mitochondrial dysfunction in an Alzheimer's disease (AD) in vitro models. Amyloid beta (Aβ) was used to induce cytotoxity in an immortal hippocampal cell line (HT22) and neuronal stem cells from the brain of TG2576 transgenic mice were also used to test the protective role of hASC cytosolic extracts. Cell viability and flow cytometry results demonstrated that the hASC extract prevents the toxicity and apoptosis in AD in vitro models. Moreover, JC-1 and MitoSoxRed staining followed by fluorescence microscopy and flow cytometry results showed that the hASC extract ameliorated the effect of Aβ-induced mitochondrial oxidative stress and reduced the mitochondrial membrane potential. Western blot result showed that hASC extract modulated mitochondria-associated proteins, such as Bax and Bcl2, and down-regulated cleaved caspase-3. In addition, hASC extract decreased Aβ generation and reversed up-regulated p53 and foxo3a protein level in AD in vitro model cell derived from TG2576 mice. Taken together, these findings implicate a protective role of the hASC extract in the Aβ-induced mitochondrial apoptosis via regulation of P53/foxo3a pathway, providing insight into the molecular mechanisms of hASC extract and a therapeutic strategy to ameliorate neuronal death induced by Aβ.
authors.affiliation: Department of Molecular Medicine, Alzheimer's Byrd Institute, University of South Florida College of Medicine, Tampa, FL, United States of America.
authors.forename: Tian
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Neurology, Biomedical Research Institute; College of Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Mijung
authors.initials: M
authors.lastname: Lee
authors.affiliation: Department of Neurology, Biomedical Research Institute; College of Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Jae-Jun
authors.initials: JJ
authors.lastname: Ban
authors.affiliation: Department of Neurology, Biomedical Research Institute; College of Medicine, Seoul National University Hospital, Seoul, Korea.|Neuroscience Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Wooseok
authors.initials: W
authors.lastname: Im
authors.affiliation: Department of Biochemistry, Seoul National University College of Medicine, Seoul, Korea.|Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Inhee
authors.initials: I
authors.lastname: Mook-Jung
authors.affiliation: Department of Neurology, Biomedical Research Institute; College of Medicine, Seoul National University Hospital, Seoul, Korea.|Protein Metabolism Medical Research Center, College of Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Manho
authors.initials: M
authors.lastname: Kim
mesh_terms: D017667:Adipocytes / Q000737:chemistry*; D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival; D003600:Cytosol / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D000071316:Forkhead Box Protein O3 / Q000378:metabolism*; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000473:pathology*; D009474:Neurons / Q000378:metabolism; D018384:Oxidative Stress; D013234:Stem Cells / Q000737:chemistry*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; C474033:FoxO3 protein, mouse; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D053148:Caspase 3