Omega 3 polyunsaturated fatty acids inhibit cell proliferation by regulating cell cycle in fad3b transgenic mouse embryonic stem cells.
Omega 3 polyunsaturated fatty acids inhibit cell proliferation by regulating cell cycle in fad3b transgenic mouse embryonic stem cells.
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欧米茄3多不饱和脂肪酸通过调节FAD3B转基因小鼠胚胎干细胞中的细胞周期来抑制细胞增殖。
DOI：
10.1186/s12944-018-0862-x
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发表时间：
2018-09-08
影响因子：
4.5
通讯作者：
Li G
中科院分区：
文献类型：
--
作者：
Wei Z;Li D;Zhu L;Yang L;Chen C;Bai C;Li G
ω 3多不饱和脂肪酸（PUFA）的摄入对人体健康很重要，与细胞增殖和分化密切相关。本研究旨在研究ω 3多不饱和脂肪酸对胚胎干细胞（ESC）增殖的影响，并探讨介导这些影响的潜在机制。在这项研究中，我们从表达fad 3b的转基因小鼠中分离出ESC。我们用气相色谱-质谱法检测了ESCs的脂肪酸组成，用流式细胞仪分析了细胞周期，用实时聚合酶链反应（PCR）和蛋白质印迹法检测了基因表达。与对照ESC相比，fad 3b中ω 3 PUFA的量显著增加。而fad 3b ESCs的生长速度较对照组慢，传代18 h后大多数细胞处于延长的G 0/G1期。因此，我们推测fad 3b的表达通过增加P21的表达，从而降低细胞周期蛋白依赖性激酶4（Cdk 4）的表达，从而抑制ESCs的细胞周期。我们发现，PD 0325901，一种P21抑制剂，预处理fad 3b ESCs，明显减弱P21对Cdk 4的抑制作用，并恢复细胞周期。fad 3b基因在胚胎干细胞中的表达增加了omega 3 PUFA的含量，这通过延长G1期来抑制细胞增殖，但并没有阻止G 0到G1或G1到S的转变。fad 3b ESCs的G1期延长可能是通过上调p21下调Cdk 4表达而引起的。这些结果表明，ω 3 PUFA在体内的积累可能有益于影响ESC的分化，并且fad 3b ESC可能是研究相关机制的有用工具。本文的在线版本（10.1186/s12944-018-0862-x）包含补充材料，可供授权用户使用。
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. 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. 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. 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. 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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DOI：
10.4161/cc.26130
发表时间：
2013-09-15
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Leontieva OV;Blagosklonny MV
通讯作者：
Blagosklonny MV
影响因子：
7.3
作者：
Cui, Pei H.;Petrovic, Nenad;Murray, Michael
通讯作者：
Murray, Michael
影响因子：
64.5
作者：
Gonzales, Kevin Andrew Uy;Liang, Hongqing;Ng, Huck-Hui
通讯作者：
Ng, Huck-Hui
影响因子：
46.9
作者：
Lai, LX;Kang, JX;Dai, YF
通讯作者：
Dai, YF
影响因子：
2.9
作者：
Danbara, N;Yuri, T;Tsubura, A
通讯作者：
Tsubura, A