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首页> 外文期刊>Journal of Cellular Physiology >High glucose increase cell cycle regulatory proteins level of mouse embryonic stem cells via PI3-K/Akt and MAPKs signal pathways.
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High glucose increase cell cycle regulatory proteins level of mouse embryonic stem cells via PI3-K/Akt and MAPKs signal pathways.

机译:高葡萄糖增加细胞周期调控蛋白质水平的老鼠胚胎干细胞通过PI3-K / Akt和MAPKs信号通路。

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摘要

This study examined the effects of high glucose on cell proliferation and its related signal pathways using mouse embryonic stem (ES) cells. Here, we showed that high glucose level significantly increased [3H]thymidine incorporation, BrdU incorporation, the number of cells, [3H]leucine, and [3H]proline incorporation in a time-( >3 hr) and dose-(> 25 mM) dependent manner. Moreover, high glucose level increased the cellular reactive oxygen species (ROS), Akt, and mitogen-activated protein kinases (MAPKs) phosphorylation. Subsequently, these signaling molecules involved in high glucose-induced increase of [3H]thymidine incorporation. High glucose level also increased cyclin D1, cyclin E, cyclin-dependent kinase (CDK) 2, and CDK 4 protein levels, which is cell cycle regulatory proteins acting in G1-S phase of cell cycle. Inhibition of phosphatidylinositol 3-kinase (PI3-K) (LY 294002: PI3-kinase inhibitor, 10(-6) M), Akt (Akt inhibitor, 10(-5) M), and p44/42 MAPKs (PD 98059: MEK inhibitor, 10(-5) M) decreased these proteins. High glucose level phosphorylated the RB protein, which was decreased by inhibition of PI3-K and Akt. In conclusion, high glucose level stimulates mouse ES cell proliferation via the PI3-K/Akt and MAPKs pathways.
机译:本研究调查了高葡萄糖的影响细胞增殖及其相关信号使用小鼠胚胎干细胞(ES)细胞通路。在这里,我们表明,高葡萄糖水平显著增加[3 h]胸苷BrdU合并,合并的数量细胞,[3 h]亮氨酸,[3 h]脯氨酸掺入在一个时间-(> 3小时)和剂量-(> 25毫米)相关的的方式。细胞活性氧(ROS),一种蛋白激酶,和增殖蛋白激酶(MAPKs)磷酸化。高glucose-induced分子参与增加[3 h]胸苷掺入。血糖水平也增加了细胞周期蛋白D1、细胞周期素E、细胞周期蛋白依赖性激酶(CDK) 2, CDK 4蛋白质含量,细胞周期调控蛋白质在细胞周期的G1-S阶段。抑制磷脂酰肌醇3-kinase(PI3-K) (LY 294002: PI3-kinase抑制剂,(sd - 10)米),一种蛋白激酶(Akt抑制剂,10(5)米),和p44/42MAPKs (PD 98059: MEK抑制剂,10(5)米)这些蛋白质减少。RB蛋白磷酸化,减少抑制PI3-K和Akt。结论高葡萄糖水平刺激老鼠通过PI3-K ES细胞增殖/ Akt和MAPKs通路。

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