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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:Vivo中血管组织中的VACM-1 / CUL5表达被水剥夺诱导,其在体外调节水上素-1浓度的表达。

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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,Cul5基因产物,当体外过表达时,具有抗增殖效果。在体内,捕获疫苗1 / cul5存在于参与水平衡调节的组织中。已经研究了靶向疫苗1 / CUL5特异性降解的蛋白质,也没有研究可能调节在这些组织中的表达的因子。为了鉴定可通过疫苗-1 cDNA误解的基因,我们进行了微阵列分析。我们的结果表明,与对照组相比,在用VACM-1 cDNA转染的COS-1细胞中,几种基因的mRNA水平降低,包括AQP1。我们的研究结果还表明,与VACM-1 cDNA转染的COS-1细胞中,与对照相比,内源AQP1蛋白在约6倍下降约6倍。为了测试VacM-1 / CUL5可以通过损害水稳态体内的条件调节的假设,如果水剥夺24μm,我们确定了24℃的水剥夺影响疫苗-1 / Cul5水平或疫苗-1 / Cul5对AQP1的影响。大鼠肠系膜中的动脉,骨骼肌和心室患者,骨骼肌和心室水平显着高,但与对照相比,大鼠骨骼肌和心室内的心室患者中缺乏大鼠的心脏缺乏大鼠。有趣的是,24℃的水剥夺通过泛素样蛋白,NEDD8,对Cullin依赖性E3连接酶活性的改变增加了疫苗-1。虽然水剥夺在肠系膜动脉中没有显着改变AQP1水平,但AQP1蛋白浓度与NEDD8改性的疫苗-1的VAC-1与NEDD8改性的疫苗相反。这些结果表明,湿湿疫苗/ CUL5可以调节体内和体外内皮AQP1浓度。

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