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作 者:张柳[1] 马慧娟 邢邯英 牛尚梅[1] 吕秀芹 宋光耀[1]
机构地区:[1]河北医科大学研究生学院河北省人民医院内分泌科河北省老年医学重点实验室,石家庄050000
出 处:《重庆医科大学学报》2017年第11期1503-1508,共6页Journal of Chongqing Medical University
基 金:国家自然科学基金资助项目(编号:81200638);河北省国际科技合作资助项目(编号:15397750D)
摘 要:目的:研究Rho信号横纹肌激活剂(the striated muscle activator of Rho signaling,STARS)在棕榈酸诱导的肌细胞胰岛素抵抗中的作用及其机制。方法:采用棕榈酸(palmitic acid,PA)孵育L6成肌细胞构建胰岛素抵抗模型,包括对照组和棕榈酸组,并通过质粒上调STARS的表达,包括对照组,空质粒组(pc DNA),STARS过表达组(pc DNA/STARS),棕榈酸组(PA),棕榈酸空质粒组(PA+pc DNA),棕榈酸STARS过表达组(PA+pc DNA/STARS),以及si RNA下调肌细胞中STARS的表达,包括对照组,si RNA阴性对照组(NC-si RNA),STARS敲低组(si-STARS),棕榈酸组(PA),棕榈酸si RNA阴性对照组(PA+NC-si RNA),棕榈酸STARS敲低组(PA+si-STARS)研究STARS在骨骼肌胰岛素抵抗中的作用以及其下游信号通路。采用RT-PCR及Western blot方法检测各组STARS、血清应答因子(serum response factor,SRF)、巨核细胞白血病因子1(megakaryoblastic leukemia 1,MKL1)、AKT、IRS-1,以及GLUT4 m RNA和蛋白表达水平。结果:与对照组相比,PA组STARS m RNA和蛋白的表达明显增加(均P=0.000);STARS上调组肌细胞STARS m RNA和蛋白表达均明显增加(均P=0.000),IRS-1(P=0.000)、GLUT4(P=0.000)和AKT m RNA(P=0.000)表达明显下降,AKT丝氨酸磷酸化水平(P=0.000)和GLUT4(P=0.000)蛋白的表达显著降低,IRS-1丝氨酸磷酸化水平显著增加。下调STARS的表达后出现了与上述相反的结果。经上述干预后,SRF和MKL1基因和蛋白水平均没有明显变化。结论:STARS与胰岛素敏感性密切相关,但其下游靶点MKL1和SRF没有变化。可能通过影响其修饰后翻译,也可能通过其他信号通路在胰岛素抵抗中发挥作用,需要进一步研究。Objective :To study the role of the striated muscle activator of Rho signaling (STARS) in insulin resistance induced by palmitic acid in muscle cells as well as the potential mechanisms modulating STARS expression. Methods:L6 myoblasts were incu2 bated with palmitic acid to establish a model for insulin resistance. The effects of STARS on insulin resistance in L6 muscle ceils were observed and its potential mechanisms of action were further explored by inducing its over-expression and knockdown. Levels of STARS, SRF, MKL1 ,AKT, IRS-1 and GLUT4 mRNA and protein were detected by RT-PCR and Western blot,respectively. Results: Compared with those in the control group,STARS mRNA and protein levels were significantly increased in muscle cells in the PA (palmitic acid) and pcDNMSTARS(STARS over-expression) groups. Levels of IRS-1 ,GLUT4 and AKT mRNA were significantly decreased in the pcDNMSTARS group. In addition, serine phosphorylation of AKT and GLUT4 protein levels were decreased and ser- ine phosphorylation of IRS-1 was increased. In contrast, STARS knockdown produced the opposite results in above parameters. MKL1 and SRF mRNA and protein levels were unaffected by these interventions. Conclusion:STARS is closely related with insulin sensi- tivity, while without significant changes of its downstream target MKL1 and SRF. It might play a role in insulin resistance by modular-ing post-translational modification of MKL1 and SRF or through other signaling pathways. Further investigations are thus needed.
关 键 词:胰岛素抵抗 肌细胞 Rho信号横纹肌激活剂 血清应答因子 巨核细胞白血病因子1 胰岛素信号通路
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