斯钙素蛋白-1和缺氧诱导因子-1α的相互作用对肾癌细胞线粒体膜电势稳定的影响  

Effects of Stanniocalcin-1 and Hypoxia-inducible Factor-1α on Mitochondrial Membrane Potential Stability in Renal Carcinoma Cells

作　　者：杨清滔[1] 谷江[1] 张永春[1] 朱致晖[1] 杨永安[1] 王楠[1] 祝庆亮[2] 

机构地区：[1]贵阳医学院附属医院泌尿外科,贵阳550004 [2]江都人民医院泌尿外科,江苏扬州225200

出　　处：《中国医学科学院学报》2014年第1期12-19,共8页Acta Academiae Medicinae Sinicae

基　　金：贵州省科技厅社会攻关计划项目(黔科合SY字[2011]3060)~~

摘　　要：目的研究斯钙素蛋白-1(STC-1)和缺氧诱导因子-1α(HIF-1α)相互作用后的调钙功能对肾癌细胞线粒体膜电势稳定的影响。方法构建高表达HIF-1α的肾癌细胞模型,采用不同浓度STC-1蛋白分别干预荷基因肾癌细胞和单纯肾癌细胞,MTT法检测细胞增殖,RT-PCR和ELISA法检测细胞内HIF-1α和STC-1的基因及蛋白表达情况,荧光探针检测细胞内Ca2+变化,荧光分光光度计检测线粒体膜电位(Δψm),紫外分光光度计检测线粒体通透性转换孔(mPTP)。结果 HIF-1α基因转染、STC-1干预及基因转染后再STC-1干预3种方式均可提高Δψm,降低细胞内Ca2+和mPTP水平,促进细胞增殖(P均<0.05),以上结果可随着STC-1浓度的增加而逐渐增强,但细胞增殖率的升高趋势却逐渐减缓。结论 HIF-1α可能通过促进STC-1表达,下调Ca2+水平,从而稳定线粒体膜电势来参与肾癌细胞的恶性增殖,但此作用亦因外源性STC-1对HIF-1α的抑制而逐渐减弱。Objective To explore the effects of stanniocalcin-1 （STC-1 ） and hypoxia-inducible factor- 1α （ HIF- 1α） on the calcium and thus on the mitochondrial membrane potential （AOm） in renal carcinoma cells. Methods We successfully established the renal carcinoma cell models with high HIF-1α gene expres- sion. After various concentrations of STC- 1 solutions were added to the culture medium, the proliferation of cells, expressions of HIF-1α and STC-1, levels of Ca^2＋, △ψm, and mPTP were detected by MTT, RT-PCR, ELISA, fluorescence spectrophotometry, and ultraviolet spectrophotometry, respectively. Results The proliferation of renal carcinoma cells and △ψm were improved after HIF-1α gene transfection, STC-1 protein interven- tion, and STC- 1 protein intervention after gene transfection. While the intracellular Ca^2＋ level and mPTP were de- creased significantly （P 〈0. 05）, all the changes were intensified with the gradual increase of STC-1. However, the increasing trend of cell proliferation gradually declined. Conclusion HIF-1α may participate in malignant proliferation of renal carcinoma cells by promoting STC-1 proliferation or down-regulating Ca^2＋ ; however, such an effect may be gradually attenuated due to the inhibitory effect of STC-1 on HIF-1α.

关 键 词：肾癌细胞 斯钙素蛋白-1 缺氧诱导因子-1Α 线粒体 

分 类 号：R445.2[医药卫生—影像医学与核医学]