Hypoxia and Hyperoxia Differentially Control Proliferation of Rat Neural Crest Stem Cells via Distinct Regulatory Pathways of the HIF1α-CXCR4 and TP53-TPM1 Proteins.

Hypoxia and Hyperoxia Differentially Control Proliferation of Rat Neural Crest Stem Cells via Distinct Regulatory Pathways of the HIF1α-CXCR4 and TP53-TPM1 Proteins.

Dev Dyn. 2016 Dec 21;:

Authors: Chen CC, Hsia CW, Ho CW, Liang CM, Chen CM, Huang KL, Kang BH, Chen YH

Abstract
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. This article is protected by copyright. All rights reserved.

PMID: 28002632 [PubMed - as supplied by publisher]

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