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Evidence of endoplasmic reticulum stress and protein synthesis inhibition in the placenta of non-native women at high altitude
Pregnancy at high altitude is associated with a reduction in birth weight of ∼100 g/1000 m of ascent. The underlying mechanisms are unclear but may involve alteration in energy-demanding activities, such as protein synthesis. To test this hypothesis, both in vivo and in vitro approaches were used. P...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Federation of American Societies for Experimental Biology
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3336782/ https://www.ncbi.nlm.nih.gov/pubmed/22267338 http://dx.doi.org/10.1096/fj.11-190082 |
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author | Yung, Hong Wa Cox, Mathew Tissot van Patot, Martha Burton, Graham J. |
author_facet | Yung, Hong Wa Cox, Mathew Tissot van Patot, Martha Burton, Graham J. |
author_sort | Yung, Hong Wa |
collection | PubMed |
description | Pregnancy at high altitude is associated with a reduction in birth weight of ∼100 g/1000 m of ascent. The underlying mechanisms are unclear but may involve alteration in energy-demanding activities, such as protein synthesis. To test this hypothesis, both in vivo and in vitro approaches were used. Placental tissues from pregnant women residing at 3100 m were studied, and placental cells were incubated under hypoxia. In the 3100-m placentas, we observed dilation of endoplasmic reticulum (ER) cisternae, increased phosphorylation of eukaryotic initiation factor 2 subunit α (P-eIF2α), reduced AKT phosphorylation, and reduced P-4E-BP1 but increased 4E-BP1 protein compared to sea level controls. These findings suggest the presence of ER stress and protein synthesis inhibition. Hypoxia (1% O(2)) reduced proliferation of trophoblast-like JEG-3 cells, BeWo cells, and placental fibroblasts by ∼40, ∼60, and ∼18%, respectively. Sublethal dosage of salubrinal, an eIF2α phosphatase inhibitor, increased P-eIF2α and reduced BeWo cell and placental fibroblast proliferation by ∼50%. Administration of the PI-3K inhibitor LY294002 also reduced JEG-3 proliferation. Our results demonstrate that exposure to chronic hypobaric hypoxia causes mild placental ER stress, which, in turn, modulates protein synthesis and slows proliferation. These effects may account for the reduced placental villous volume, and contribute to the low birth weight that typifies high-altitude populations.—Yung, H. W., Cox, M., Tissot van Patot, M., Burton, G. J. Evidence of endoplasmic reticulum stress and protein synthesis inhibition in the placenta of non-native women at high altitude. |
format | Online Article Text |
id | pubmed-3336782 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Federation of American Societies for Experimental Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-33367822012-05-07 Evidence of endoplasmic reticulum stress and protein synthesis inhibition in the placenta of non-native women at high altitude Yung, Hong Wa Cox, Mathew Tissot van Patot, Martha Burton, Graham J. FASEB J Research Communications Pregnancy at high altitude is associated with a reduction in birth weight of ∼100 g/1000 m of ascent. The underlying mechanisms are unclear but may involve alteration in energy-demanding activities, such as protein synthesis. To test this hypothesis, both in vivo and in vitro approaches were used. Placental tissues from pregnant women residing at 3100 m were studied, and placental cells were incubated under hypoxia. In the 3100-m placentas, we observed dilation of endoplasmic reticulum (ER) cisternae, increased phosphorylation of eukaryotic initiation factor 2 subunit α (P-eIF2α), reduced AKT phosphorylation, and reduced P-4E-BP1 but increased 4E-BP1 protein compared to sea level controls. These findings suggest the presence of ER stress and protein synthesis inhibition. Hypoxia (1% O(2)) reduced proliferation of trophoblast-like JEG-3 cells, BeWo cells, and placental fibroblasts by ∼40, ∼60, and ∼18%, respectively. Sublethal dosage of salubrinal, an eIF2α phosphatase inhibitor, increased P-eIF2α and reduced BeWo cell and placental fibroblast proliferation by ∼50%. Administration of the PI-3K inhibitor LY294002 also reduced JEG-3 proliferation. Our results demonstrate that exposure to chronic hypobaric hypoxia causes mild placental ER stress, which, in turn, modulates protein synthesis and slows proliferation. These effects may account for the reduced placental villous volume, and contribute to the low birth weight that typifies high-altitude populations.—Yung, H. W., Cox, M., Tissot van Patot, M., Burton, G. J. Evidence of endoplasmic reticulum stress and protein synthesis inhibition in the placenta of non-native women at high altitude. Federation of American Societies for Experimental Biology 2012-05 /pmc/articles/PMC3336782/ /pubmed/22267338 http://dx.doi.org/10.1096/fj.11-190082 Text en © FASEB This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/us/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Communications Yung, Hong Wa Cox, Mathew Tissot van Patot, Martha Burton, Graham J. Evidence of endoplasmic reticulum stress and protein synthesis inhibition in the placenta of non-native women at high altitude |
title | Evidence of endoplasmic reticulum stress and protein synthesis inhibition in the placenta of non-native women at high altitude |
title_full | Evidence of endoplasmic reticulum stress and protein synthesis inhibition in the placenta of non-native women at high altitude |
title_fullStr | Evidence of endoplasmic reticulum stress and protein synthesis inhibition in the placenta of non-native women at high altitude |
title_full_unstemmed | Evidence of endoplasmic reticulum stress and protein synthesis inhibition in the placenta of non-native women at high altitude |
title_short | Evidence of endoplasmic reticulum stress and protein synthesis inhibition in the placenta of non-native women at high altitude |
title_sort | evidence of endoplasmic reticulum stress and protein synthesis inhibition in the placenta of non-native women at high altitude |
topic | Research Communications |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3336782/ https://www.ncbi.nlm.nih.gov/pubmed/22267338 http://dx.doi.org/10.1096/fj.11-190082 |
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