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作 者:赵凌宇[1,2] 焦倩[1] 郭波[2] 杨蓬勃[1] 陈新林[1] 刘勇[1]
机构地区:[1]西安交通大学医学院神经生物研究所,西安710061 [2]西安交通大学医学院遗传学与分子生物学系,西安710061
出 处:《神经解剖学杂志》2014年第1期7-12,共6页Chinese Journal of Neuroanatomy
基 金:国家自然科学基金(81070998)
摘 要:目的:研究代谢型谷氨酶受体mGluR5特异性激动剂CHPG对人胚胎皮质神经干细胞(NSCs)增殖的影响以及分子机制。方法:采用MTT比色法和神经球直径测量分析CHPG对人NSCs增殖的影响;流式细胞仪分析对细胞周期和细胞凋亡的影响;采用免疫蛋白印迹法,观察磷酸化ERK,JNK和p38 MAPKs表达水平的变化。结果:mGluR5激动剂CHPG促进人胚胎皮质NSCs增殖;CHPG组与对照组相比,S期与G2/M期细胞数量显著增加(P<0.05),G1/G0期细胞数量显著减少(P<0.05);CHPG组早期凋亡和晚期凋亡细胞显著减少(P<0.05);CHPG组与对照组相比,ERK1/2和JNK2的磷酸化水平显著增高,但是p38 MAPKs的磷酸化水平显著降低(P<0.01)。结论:mGluR5激动剂CHPG促进人胚胎皮质NSCs增殖,同时伴随着ERK和JNK的磷酸化激活。Objective: To investigate the effects of metabotropic slutamate receptor mGluR5 specific agonist CHPG on the proliferation of human embryonic cortical neural stem cells (NSCs) and the related molecular mechanism. Methods: MTF assay and diameter measuring of neurospheres were used to analyze the effects of mGluR5 agonist CHPG on prolifera- tion of human embryonic NSCs. The effects of mGluR5 agonist CHPG on the cell cycle and apoptosis of human NSCs were analyzed with flow eytometer. The expression of phosphorylated ERK, JNK and p38 MAPKs in human NSCs were exam- ined with Western Blot after mGluR5 agonist CHPG treatment. Results: mGluR5 agonist CHPG promoted proliferation of human embryonic cortical NSCs. The number of cells in S and G2/M phass significantly increased in CHPG groups com- pared to that of the control group (P 〈0.05 ) , meanwhile the number of cells in G1/G0 phase remarkably decreased (P 〈 0.05 ) ; the percentage of early and late apoptic cells significantly decreased in CHPG groups ( P 〈 0.05 ). It was found that p-ERK1/2 and p-JNK2 levels significantly increased in agonist CHPG group compared to that of control group, but p- p38 remarkably decreased (P 〈 0.01 ). Conclusion: mGluR5 agonist CHPG promotes proliferation of human embryonic cortical NSCs with activation of mitogen-activated protein kinases signaling pathway.
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