title: Modulation of mitochondrial function by stem cell-derived cellular components.
abstract: Huntington's disease (HD) is the most common hereditary neurodegenerative diseases, in which the loss of striatal neuron caused by the aggregation of mutant huntingtin protein (mHtt) is the main pathological feature. Our previous studies have demonstrated that human adipose stem cells (hASC) and its extracts can slow down the progression of HD in vitro and in vivo. hASC are readily accessible adult stem cells, and the cytosolic extracts contain a number of neurotrophic factors. Here, we further explored the role of the hASC extracts in neuronal death and mitochondrial function in HD. Our results showed that the hASC extracts prevent mHtt-induced cell toxicity and cell apoptosis. Moreover, the hASC extracts recovered mHtt-induced mitochondrial oxidative stress and reduced mitochondrial membrane potential. The hASC extracts blocked the interaction between p53 and mHtt, and decreased the endogenous p53 levels at both transcriptional and post-translational levels, resulting in the instability of p53 and increased neuronal survival. Taken together, these findings implicate protective roles of hASC extracts in mHtt-induced mitochondrial apoptosis, providing insights into the molecular mechanism of the hASC in the therapeutic strategy of HD.
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Tian
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Neurology, Laboratory for Neurotherapeutics, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Wooseok
authors.initials: W
authors.lastname: Im
authors.affiliation: Department of Neurology, Laboratory for Neurotherapeutics, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Soon-Tae
authors.initials: ST
authors.lastname: Lee
authors.affiliation: Department of Neurology, Laboratory for Neurotherapeutics, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Jae-Jun
authors.initials: JJ
authors.lastname: Ban
authors.affiliation: Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Ye Jin
authors.initials: YJ
authors.lastname: Chai
authors.affiliation: Department of Neurology, Laboratory for Neurotherapeutics, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Mijung
authors.initials: M
authors.lastname: Lee
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Biochemistry, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Inhee
authors.initials: I
authors.lastname: Mook-Jung
authors.affiliation: Department of Neurology, Laboratory for Neurotherapeutics, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea. Electronic address: stemcell.snu@gmail.com.
authors.forename: Kon
authors.initials: K
authors.lastname: Chu
authors.affiliation: Department of Neurology, Laboratory for Neurotherapeutics, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea. Electronic address: kimmanho@snu.ac.kr.
authors.forename: Manho
authors.initials: M
authors.lastname: Kim
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D053687:Adult Stem Cells / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002457:Cell Extracts / Q000494:pharmacology; D002460:Cell Line; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D039902:Multipotent Stem Cells / Q000378:metabolism; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D002457:Cell Extracts; C086055:HTT protein, human; D000071058:Huntingtin Protein; D050505:Mutant Proteins; D009419:Nerve Tissue Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: Apoptosis; Human adipose stem cells; Mitochondria; Mutant huntingtin; p53