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Omega 3 polyunsaturated fatty acids inhibit cell proliferation by regulating cell cycle in fad3b transgenic mouse embryonic stem cells

BACKGROUND: The consumption of omega 3 polyunsaturated fatty acids (PUFAs) is important for human health and is closely associated with cell proliferation and differentiation. This study aimed to investigate the influence of omega 3 PUFAs on embryonic stem cell (ESC) proliferation and explore potent...

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Autores principales: Wei, Zhuying, Li, Dongfang, Zhu, Lin, Yang, Lei, Chen, Chen, Bai, Chunling, Li, Guangpeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6129006/
https://www.ncbi.nlm.nih.gov/pubmed/30193583
http://dx.doi.org/10.1186/s12944-018-0862-x
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author Wei, Zhuying
Li, Dongfang
Zhu, Lin
Yang, Lei
Chen, Chen
Bai, Chunling
Li, Guangpeng
author_facet Wei, Zhuying
Li, Dongfang
Zhu, Lin
Yang, Lei
Chen, Chen
Bai, Chunling
Li, Guangpeng
author_sort Wei, Zhuying
collection PubMed
description BACKGROUND: The consumption of omega 3 polyunsaturated fatty acids (PUFAs) is important for human health and is closely associated with cell proliferation and differentiation. This study aimed to investigate the influence of omega 3 PUFAs on embryonic stem cell (ESC) proliferation and explore potential mechanisms that mediate these effects. METHODS: In this study, we isolated ESCs from fad3b-expressing transgenic mice. We detected the fatty-acid composition of ESCs using gas chromatography-mass spectroscopy, analyzed cell-cycle phases using flow cytometry, and detected gene expression using real-time polymerase chain reaction (PCR) and western blots. RESULTS: The amount of omega 3 PUFAs significantly increased in fad3b versus control ESCs. However, the growth of fad3b ESCs was slower than that of control cells, and most fad3b ESCs were in a prolonged G0/G1 phase after being passaged for 18 h. Therefore, we hypothesized that fad3b expression inhibited the cell cycle in ESCs by increasing the expression of P21, which then decreased the expression of cyclin-dependent kinase 4 (Cdk4). We found that pretreatment of fad3b ESCs with PD0325901, a P21 inhibitor, clearly attenuated the inhibitory effects of P21 on Cdk4, and resumed the cell cycle. CONCLUSIONS: Expression of the fad3b gene in ESCs increased the omega 3 PUFA content, which inhibited cell proliferation by prolonging the G1 phase but did not arrest the G0-to-G1 or G1-to-S transitions. The prolonged G1 phase in fad3b ESCs was probably induced by downregulation of Cdk4 expression via p21 upregulation. These results suggest that accumulation of omega 3 PUFAs in vivo may beneficially affect ESC differentiation and that fad3b ESCs may be a useful tool for investigating related mechanisms. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12944-018-0862-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-61290062018-09-10 Omega 3 polyunsaturated fatty acids inhibit cell proliferation by regulating cell cycle in fad3b transgenic mouse embryonic stem cells Wei, Zhuying Li, Dongfang Zhu, Lin Yang, Lei Chen, Chen Bai, Chunling Li, Guangpeng Lipids Health Dis Research BACKGROUND: The consumption of omega 3 polyunsaturated fatty acids (PUFAs) is important for human health and is closely associated with cell proliferation and differentiation. This study aimed to investigate the influence of omega 3 PUFAs on embryonic stem cell (ESC) proliferation and explore potential mechanisms that mediate these effects. METHODS: In this study, we isolated ESCs from fad3b-expressing transgenic mice. We detected the fatty-acid composition of ESCs using gas chromatography-mass spectroscopy, analyzed cell-cycle phases using flow cytometry, and detected gene expression using real-time polymerase chain reaction (PCR) and western blots. RESULTS: The amount of omega 3 PUFAs significantly increased in fad3b versus control ESCs. However, the growth of fad3b ESCs was slower than that of control cells, and most fad3b ESCs were in a prolonged G0/G1 phase after being passaged for 18 h. Therefore, we hypothesized that fad3b expression inhibited the cell cycle in ESCs by increasing the expression of P21, which then decreased the expression of cyclin-dependent kinase 4 (Cdk4). We found that pretreatment of fad3b ESCs with PD0325901, a P21 inhibitor, clearly attenuated the inhibitory effects of P21 on Cdk4, and resumed the cell cycle. CONCLUSIONS: Expression of the fad3b gene in ESCs increased the omega 3 PUFA content, which inhibited cell proliferation by prolonging the G1 phase but did not arrest the G0-to-G1 or G1-to-S transitions. The prolonged G1 phase in fad3b ESCs was probably induced by downregulation of Cdk4 expression via p21 upregulation. These results suggest that accumulation of omega 3 PUFAs in vivo may beneficially affect ESC differentiation and that fad3b ESCs may be a useful tool for investigating related mechanisms. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12944-018-0862-x) contains supplementary material, which is available to authorized users. BioMed Central 2018-09-08 /pmc/articles/PMC6129006/ /pubmed/30193583 http://dx.doi.org/10.1186/s12944-018-0862-x Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Wei, Zhuying
Li, Dongfang
Zhu, Lin
Yang, Lei
Chen, Chen
Bai, Chunling
Li, Guangpeng
Omega 3 polyunsaturated fatty acids inhibit cell proliferation by regulating cell cycle in fad3b transgenic mouse embryonic stem cells
title Omega 3 polyunsaturated fatty acids inhibit cell proliferation by regulating cell cycle in fad3b transgenic mouse embryonic stem cells
title_full Omega 3 polyunsaturated fatty acids inhibit cell proliferation by regulating cell cycle in fad3b transgenic mouse embryonic stem cells
title_fullStr Omega 3 polyunsaturated fatty acids inhibit cell proliferation by regulating cell cycle in fad3b transgenic mouse embryonic stem cells
title_full_unstemmed Omega 3 polyunsaturated fatty acids inhibit cell proliferation by regulating cell cycle in fad3b transgenic mouse embryonic stem cells
title_short Omega 3 polyunsaturated fatty acids inhibit cell proliferation by regulating cell cycle in fad3b transgenic mouse embryonic stem cells
title_sort omega 3 polyunsaturated fatty acids inhibit cell proliferation by regulating cell cycle in fad3b transgenic mouse embryonic stem cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6129006/
https://www.ncbi.nlm.nih.gov/pubmed/30193583
http://dx.doi.org/10.1186/s12944-018-0862-x
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