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首页> 外文期刊>Cell and Tissue Research >VACM-1/cul5 expression in vascular tissue in vivo is induced by water deprivation and its expression in vitro regulates aquaporin-1 concentrations
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VACM-1/cul5 expression in vascular tissue in vivo is induced by water deprivation and its expression in vitro regulates aquaporin-1 concentrations

机译:缺水诱导体内血管组织中VACM-1 / cul5的表达,其在体外的表达调节aquaporin-1的浓度

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摘要

VACM-1, a cul5 gene product, when overexpressed in vitro, has an antiproliferative effect. In vivo, VACM-1/cul5 is present in tissues involved in the regulation of water balance. Neither proteins targeted for VACM-1/cul5-specific degradation nor factors that may regulate its expression in those tissues have been studied. To identify genes that may be misregulated by VACM-1 cDNA, we performed microarray analysis. Our results indicate that in cos-1 cells transfected with VACM-1 cDNA, mRNA levels for several genes, including AQP1, were decreased when compared to the control group. Our results also indicate that in cos-1 cells transfected with VACM-1 cDNA, endogenous AQP1 protein was decreased about 6-fold when compared to the controls. To test the hypothesis that VACM-1/cul5 may be regulated by conditions that compromise water homeostasis in vivo, we determined if 24 h of water deprivation affects VACM-1/cul5 levels or the effect of VACM-1/cul5 on AQP1. VACM-1 mRNA and protein levels were significantly higher in rat mesenteric arteries, skeletal muscle and the heart ventricle but not in the heart atrium from 24-h water-deprived rats when compared to the controls. Interestingly, 24 h of water deprivation increased modification of VACM-1 by an ubiquitin-like protein, Nedd8, essential for cullin-dependent E3 ligase activity. Although water deprivation did not significantly change AQP1 levels in the mesenteric arteries, AQP1 protein concentrations were inversely correlated with the ratio of the VACM-1 to Nedd8-modified VACM-1. These results suggest that VACM-1/cul5 may regulate endothelial AQP1 concentration both in vivo and in vitro.
机译:VACM-1是cul5基因的产物,在体外过表达时具有抗增殖作用。在体内,VACM-1 / cul5存在于参与调节水平衡的组织中。既没有研究针对VACM-1 / cul5特异性降解的蛋白质,也没有研究可能调节其在这些组织中表达的因子。为了鉴定可能被VACM-1 cDNA调控的基因,我们进行了微阵列分析。我们的结果表明,在用VACM-1 cDNA转染的cos-1细胞中,与对照组相比,包括AQP1在内的几种基因的mRNA水平降低了。我们的结果还表明,在用VACM-1 cDNA转染的cos-1细胞中,与对照相比,内源性AQP1蛋白降低了约6倍。为了检验VACM-1 / cul5可能受损害体内体内水稳态的条件调节的假说,我们确定了缺水24小时是否会影响VACM-1 / cul5水平或VACM-1 / cul5对AQP1的影响。与对照组相比,在24小时缺水的大鼠中,大鼠肠系膜动脉,骨骼肌和心室中的VACM-1 mRNA和蛋白水平显着较高,但在心房中则没有。有趣的是,缺水的24小时增加了泛素样蛋白Nedd8对VACM-1的修饰,该蛋白对cullin依赖E3连接酶的活性至关重要。尽管缺水并没有明显改变肠系膜动脉中的AQP1水平,但AQP1蛋白浓度与VACM-1与Nedd8修饰的VACM-1的比例成反比。这些结果表明,VACM-1 / cul5可以在体内和体外调节内皮AQP1的浓度。

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