VACM-1/cul5 expression in vascular tissue in vivo is induced by water deprivation and its expression in vitro regulates aquaporin-1 concentrations
Autor: | Gary L. Dewey, Bradley T. Andresen, Isabelle P. Le, Shirley E. Bradley Dean, Joseph L. Stodola, Inara B. Lazdins, Pete Haak, Maria A. Burnatowska-Hledin, Travis R. Ruch, Alyssa E. Johnson, James H. Resau, Ashleigh Sartor, Christopher C. Barney |
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Rok vydání: | 2012 |
Předmět: |
Male
Receptors Vasopressin Histology Endogeny Biology Transfection Pathology and Forensic Medicine Rats Sprague-Dawley Gene product In vivo Complementary DNA Chlorocebus aethiops medicine Animals RNA Messenger Receptor Ubiquitins Mesenteric arteries Regulation of gene expression Aquaporin 1 Water Deprivation Myocardium Water Cell Biology Cullin Proteins Molecular biology Mesenteric Arteries Rats Cell biology medicine.anatomical_structure Gene Expression Regulation COS Cells Female Rabbits |
Zdroj: | Cell and Tissue Research. 349:527-539 |
ISSN: | 1432-0878 0302-766X |
Popis: | 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. |
Databáze: | OpenAIRE |
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