Hypoxia and hyperoxia differentially control proliferation of rat neural crest stem cells via distinct regulatory pathways of the HIF1α-CXCR4 and TP53-TPM1 proteins

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• 作者：Chien-Cheng Chen ; Ching-Wu Hsia ; Cheng-Wen Ho ; Chang-Min Liang ; Chieh-Min Chen ; Kun-Lun Huang ; Bor-Hwang Kang and Yi-Hui Chen
• 刊名：Developmental Dynamics
• 出版年：2017
• 出版时间：March 2017
• 年：2017
• 卷：246
• 期：3
• 页码：162-185
• 全文大小：1888K
• ISSN：1097-0177

文摘

Background: 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. Results: 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. Conclusions: 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.