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Title: Expression of hypoxia-inducible factor-1 by trophectoderm cells in response to hypoxia and epidermal growth factor

Abstract

The low oxygen environment in the uterine environment requires pre-implantation embryos to adapt to oxygen deficiency. Hypoxia-inducible factor (HIF)-1 is a master regulator whereby cells adapt to changes in oxygen concentrations. In addition to hypoxic conditions, non-hypoxic stimuli such as growth factors also activate expression of HIF-1. In this study, the mechanisms underlying low oxygen-dependent and epidermal growth factor (EGF)-dependent expression of HIF-1α were explored using porcine trophectoderm (pTr) cells. The results indicated that expression of HIF-1α and HIF-1β mRNAs was not affected by low concentrations of oxygen; however, hypoxic conditions markedly increased the abundance of HIF-1α protein, especially in nuclei of pTr cells. Even under normoxic conditions, the abundance of HIF-1α protein increased in response to EGF. This EGF-mediated increase in HIF-1α protein was blocked through inhibition of translation by cycloheximide. The inhibitors LY294002 (PI3K-AKT inhibitor), U0126 (inhibitor of ERK1/2) and rapamycin (mTOR inhibitor) also blocked the ability of EGF to increase HIF-1α protein and to phosphorylate AKT, ERK1/2 and mTOR proteins. Both hypoxia and EGF induced proliferation of pTr cells. This ability of EGF to stimulate proliferation of pTr cells was suppressed by EGFR siRNA, but not HIF-1α siRNA, but a significant decrease in EGF-induced HIF-1α protein occurredmore » when pTr cells were transfected with HIF-1α siRNA. The results of the present study suggest that pTr cells adapt to oxygen deficiency and proliferate in response to an oxygen-dependent HIF-1 system, and that EGF at maternal–conceptus interface can increase the abundance of HIF-1α protein via translational regulation through AKT, ERK1/2 and mTOR signaling cascades. - Highlights: • HIF-1α expression is up-regulated in pTr cells under low oxygen concentrations. • EGF induces HIF-1α accumulation in pTr cells. • EGF-induced HIF-1α accumulation is blocked by de-novo translation inhibitor. • EGF-induced HIF-1α accumulation is mediated by AKT, ERK1/2 and mTOR pathways. • Oxygen deficiency and EGF has stimulatory effect on proliferation of pTr cells.« less

Authors:
 [1];  [2];  [3];  [1]
  1. Department of Animal Resources Science, Dankook University, Cheonan (Korea, Republic of)
  2. Center for Animal Biotechnology and Genomics and Department of Animal Science, Texas A&M University, College Station, TX (United States)
  3. Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul (Korea, Republic of)
Publication Date:
OSTI Identifier:
22594162
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 469; Journal Issue: 2; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ABUNDANCE; ANOXIA; CELL PROLIFERATION; CONCENTRATION RATIO; CYCLOHEXIMIDE; GROWTH FACTORS; MESSENGER-RNA; OXYGEN

Citation Formats

Jeong, Wooyoung, Bazer, Fuller W., Song, Gwonhwa, and Kim, Jinyoung. Expression of hypoxia-inducible factor-1 by trophectoderm cells in response to hypoxia and epidermal growth factor. United States: N. p., 2016. Web. doi:10.1016/J.BBRC.2015.11.091.
Jeong, Wooyoung, Bazer, Fuller W., Song, Gwonhwa, & Kim, Jinyoung. Expression of hypoxia-inducible factor-1 by trophectoderm cells in response to hypoxia and epidermal growth factor. United States. https://doi.org/10.1016/J.BBRC.2015.11.091
Jeong, Wooyoung, Bazer, Fuller W., Song, Gwonhwa, and Kim, Jinyoung. 2016. "Expression of hypoxia-inducible factor-1 by trophectoderm cells in response to hypoxia and epidermal growth factor". United States. https://doi.org/10.1016/J.BBRC.2015.11.091.
@article{osti_22594162,
title = {Expression of hypoxia-inducible factor-1 by trophectoderm cells in response to hypoxia and epidermal growth factor},
author = {Jeong, Wooyoung and Bazer, Fuller W. and Song, Gwonhwa and Kim, Jinyoung},
abstractNote = {The low oxygen environment in the uterine environment requires pre-implantation embryos to adapt to oxygen deficiency. Hypoxia-inducible factor (HIF)-1 is a master regulator whereby cells adapt to changes in oxygen concentrations. In addition to hypoxic conditions, non-hypoxic stimuli such as growth factors also activate expression of HIF-1. In this study, the mechanisms underlying low oxygen-dependent and epidermal growth factor (EGF)-dependent expression of HIF-1α were explored using porcine trophectoderm (pTr) cells. The results indicated that expression of HIF-1α and HIF-1β mRNAs was not affected by low concentrations of oxygen; however, hypoxic conditions markedly increased the abundance of HIF-1α protein, especially in nuclei of pTr cells. Even under normoxic conditions, the abundance of HIF-1α protein increased in response to EGF. This EGF-mediated increase in HIF-1α protein was blocked through inhibition of translation by cycloheximide. The inhibitors LY294002 (PI3K-AKT inhibitor), U0126 (inhibitor of ERK1/2) and rapamycin (mTOR inhibitor) also blocked the ability of EGF to increase HIF-1α protein and to phosphorylate AKT, ERK1/2 and mTOR proteins. Both hypoxia and EGF induced proliferation of pTr cells. This ability of EGF to stimulate proliferation of pTr cells was suppressed by EGFR siRNA, but not HIF-1α siRNA, but a significant decrease in EGF-induced HIF-1α protein occurred when pTr cells were transfected with HIF-1α siRNA. The results of the present study suggest that pTr cells adapt to oxygen deficiency and proliferate in response to an oxygen-dependent HIF-1 system, and that EGF at maternal–conceptus interface can increase the abundance of HIF-1α protein via translational regulation through AKT, ERK1/2 and mTOR signaling cascades. - Highlights: • HIF-1α expression is up-regulated in pTr cells under low oxygen concentrations. • EGF induces HIF-1α accumulation in pTr cells. • EGF-induced HIF-1α accumulation is blocked by de-novo translation inhibitor. • EGF-induced HIF-1α accumulation is mediated by AKT, ERK1/2 and mTOR pathways. • Oxygen deficiency and EGF has stimulatory effect on proliferation of pTr cells.},
doi = {10.1016/J.BBRC.2015.11.091},
url = {https://www.osti.gov/biblio/22594162}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 2,
volume = 469,
place = {United States},
year = {Fri Jan 08 00:00:00 EST 2016},
month = {Fri Jan 08 00:00:00 EST 2016}
}