Cytosolic Extract of Human Adipose Stem Cells Reverses the Amyloid Beta-Induced Mitochondrial Apoptosis via P53/Foxo3a Pathway

• Published in: PloS one Vol. 12; no. 1; p. e0168859
• Main Authors: Liu, Tian, Lee, Mijung, Ban, Jae-Jun, Im, Wooseok, Mook-Jung, Inhee, Kim, Manho
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 03.01.2017; Public Library of Science (PLoS)
• Subjects: Adipocytes - chemistry; Adipose tissue; Alzheimer Disease - metabolism; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Animal cognition; Animal models; Animals; Apoptosis; Bans; BAX protein; Biology and Life Sciences; Biomedical research; Brain; Brain research; Brain stem; Caspase; Caspase 3 - metabolism; Caspase-3; Cell culture; Cell Survival; Cytometry; Cytosol - chemistry; Disorders; Endoplasmic reticulum; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Fluorescence; Fluorescence microscopy; Forkhead Box Protein O3 - metabolism; FOXO3 protein; Gene Expression Regulation; Hippocampus; Hippocampus - metabolism; Hospitals; Humans; Medicine; Medicine and Health Sciences; Membrane potential; Mice; Mice, Transgenic; Microscopy; Microscopy, Fluorescence; Mitochondria; Mitochondria - pathology; Molecular modelling; Morphology; Neurobiology; Neurodegeneration; Neurodegenerative diseases; Neurology; Neurons; Neurons - metabolism; Neurosciences; Oxidative Stress; p53 Protein; Physiological aspects; Physiological research; Proteins; Research and Analysis Methods; Stem cell transplantation; Stem cells; Stem Cells - chemistry; Toxicity; Transgenic mice; Traumatic brain injury; Tumor Suppressor Protein p53 - metabolism
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0168859

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.