title: Hypoxia and hyperoxia differentially control proliferation of rat neural crest stem cells via distinct regulatory pathways of the HIF1α-CXCR4 and TP53-TPM1 proteins.
abstract: Neural crest stem cells (NCSCs) are a population of adult multipotent stem cells. We are interested in studying whether oxygen tensions affect the capability of NCSCs to self-renew and repair damaged tissues. NCSCs extracted from the hair follicle bulge region of the rat whisker pad were cultured in vitro under different oxygen tensions.
  
  
  
  We found significantly increased and decreased rates of cell proliferation in rat NCSCs (rNCSCs) cultured, respectively, at 0.5% and 80% oxygen levels. At 0.5% oxygen, the expression of both hypoxia-inducible factor (HIF) 1α and CXCR4 was greatly enhanced in the rNCSC nuclei and was suppressed by incubation with the CXCR4-specific antagonist AMD3100. In addition, the rate of cell apoptosis in the rNCSCs cultured at 80% oxygen was dramatically increased, associated with increased nuclear expression of TP53, decreased cytoplasmic expression of TPM1 (tropomyosin-1), and increased nuclear-to-cytoplasmic translocation of S100A2. Incubation of rNCSCs with the antioxidant N-acetylcysteine (NAC) overcame the inhibitory effect of 80% oxygen on proliferation and survival of rNCSCs.
  
  
  
  Our results show for the first time that extreme oxygen tensions directly control NCSC proliferation differentially via distinct regulatory pathways of proteins, with hypoxia via the HIF1α-CXCR4 pathway and hyperoxia via the TP53-TPM1 pathway. Developmental Dynamics 246:162-185, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Graduate Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Neihu District, Taipei City, Taiwan.
authors.forename: Chien-Cheng
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Department of Finance, School of Management, Shih Hsin University, Wenshan District, Taipei City, Taiwan.
authors.forename: Ching-Wu
authors.initials: CW
authors.lastname: Hsia
authors.affiliation: Graduate Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Neihu District, Taipei City, Taiwan.|Division of Rehabilitation Medicine, Taoyuan Armed Forces General Hospital, Longtan District, Taoyuan City, Taiwan.
authors.forename: Cheng-Wen
authors.initials: CW
authors.lastname: Ho
authors.affiliation: Department of Ophthalmology, Tri-Service General Hospital, Neihu District, Taipei City, Taiwan.
authors.forename: Chang-Min
authors.initials: CM
authors.lastname: Liang
authors.affiliation: Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Neihu District, Taipei City, Taiwan.
authors.forename: Chieh-Min
authors.initials: CM
authors.lastname: Chen
authors.affiliation: Graduate Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Neihu District, Taipei City, Taiwan.|Department of Undersea and Hyperbaric Medicine, Tri-Service General Hospital, Neihu District, Taipei City, Taiwan.
authors.forename: Kun-Lun
authors.initials: KL
authors.lastname: Huang
authors.affiliation: Division of Diving Medicine, Zuoying Branch of Kaohsiung Armed Forces General Hospital, Zuoying District, Kaohsiung City, Taiwan.|Department of Otorhinolaryngology - Head and Neck Surgery, Tri-Service General Hospital, Taipei City, Taiwan.
authors.forename: Bor-Hwang
authors.initials: BH
authors.lastname: Kang
authors.affiliation: Graduate Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Neihu District, Taipei City, Taiwan.
authors.forename: Yi-Hui
authors.initials: YH
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D015153:Blotting, Western; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D018859:Hair Follicle / Q000166:cytology / Q000378:metabolism; D018496:Hyperoxia / Q000378:metabolism* / Q000503:physiopathology; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D009432:Neural Crest / Q000166:cytology*; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014335:Tropomyosin / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: C486264:Cxcr4 protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D034741:RNA, Small Interfering; D019718:Receptors, CXCR4; C490773:Tpm1 protein, rat; D014335:Tropomyosin; D016159:Tumor Suppressor Protein p53
keywords: CDKN1A (p21CIP1/WAF1); CXCR4; HIF1α; S100A2; TP53; TPM1 (tropomyosin-1); antioxidant; hyperoxia; hypoxia; neural crest; oxygen; stem cells