title: Hypoxia induces adipocyte differentiation of adipose-derived stem cells by triggering reactive oxygen species generation.
abstract: Generation of reactive oxygen species (ROS) by NADPH oxidase 4 (Nox4) induces the proliferation and migration of adipose-derived stem cells (ASCs). However, the functional role of mitochondrial ROS (mtROS) generation in ASCs is unknown. Therefore, we have investigated whether hypoxia induces the differentiation of ASCs via ROS generation. We also have tried to identify the cellular mechanisms of ROS generation underlying adipocyte differentiation. Hypoxia (2%) and ROS generators, such as antimycin and rotenone, induced adipocyte differentiation, which was attenuated by an ROS scavenger. Although Nox4 generates ROS and regulates proliferation of ASCs, Nox4 inhibition or Nox4 silencing did not inhibit adipocyte differentiation; indeed fluorescence intensity of mito-SOX increased in hypoxia, and treatment with mito-CP, a mtROS scavenger, significantly reduced hypoxia-induced adipocyte differentiation. Phosphorylation of Akt and mTOR was induced by hypoxia, while inhibition of these molecules prevented adipocyte differentiation. Thus hypoxia induces adipocyte differentiation by mtROS generation, and the PI3K/Akt/mTOR pathway is involved.
authors: Department of Applied Bioscience, CHA University, Seoul, Korea; Stem Cell Research Laboratory, CHA Stem Cell Institute, Seoul, Korea.
authors: Ji Hye
authors: JH
authors: Kim
authors: Seok-Ho
authors: SH
authors: Kim
authors: Seung Yong
authors: SY
authors: Song
authors: Won-Serk
authors: WS
authors: Kim
authors: Sun U
authors: SU
authors: Song
authors: TacGhee
authors: T
authors: Yi
authors: Myung-Shin
authors: MS
authors: Jeon
authors: Hyung-Min
authors: HM
authors: Chung
authors: Ying
authors: Y
authors: Xia
authors: Jong-Hyuk
authors: JH
authors: Sung
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000968:Antimycin A / Q000031:analogs & derivatives / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D015687:Cell Hypoxia; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003497:Cyclic N-Oxides / Q000737:chemistry / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012402:Rotenone / Q000494:pharmacology; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D000968:Antimycin A; D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; D009943:Organophosphorus Compounds; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D017382:Reactive Oxygen Species; D012402:Rotenone; D058570:TOR Serine-Threonine Kinases; C571715:mito-carboxy proxyl; C032456:antimycin; C498910:NOX4 protein, human
keywords: adipocyte differentiation; adipose-derived stem cells; hypoxia; mitochondria; reactive oxygen species