杉本 研
   Department     ,
   Position  
Article types 原著
Language English
Peer review Peer reviewed
Title Salt-inducible kinase 1 influences Na(+),K(+)-ATPase activity in vascular smooth muscle cells and associates with variations in blood pressure.
Journal Formal name:Journal of hypertension
Abbreviation:J Hypertens
ISSN code:14735598/02636352
Domestic / ForeginForegin
Volume, Issue, Page 29(12),2395-2403頁
Author and coauthor Popov Sergej, Silveira Angela, Wågsäter Dick, Takemori Hiroshi, Oguro Ryousuke, Matsumoto Sachiko, Sugimoto Ken, Kamide Kei, Hirose Takuo, Satoh Michihiro, Metoki Hirohito, Kikuya Masahiro, Ohkubo Takayoshi, Katsuya Tomohiro, Rakugi Hiromi, Imai Yutaka, Sanchez Fabio, Leosdottir Margret, Syvänen Ann-Christine, Hamsten Anders, Melander Olle, Bertorello Alejandro M
Publication date 2011/12
Summary OBJECTIVES:Essential hypertension is a complex condition whose cause involves the interaction of multiple genetic and environmental factors such as salt intake. Salt-inducible kinase 1 (SIK1) is a sucrose-nonfermenting-like kinase isoform that belongs to the AMPK (5' adenosine monophosphate-activated protein kinase) family. SIK1 activity is increased by high salt intake and plays an essential role in regulating the plasma membrane Na(+),K(+)-ATPase. The objective of this study was to examine whether SIK1 is present in vascular smooth muscle cells (VSMCs) and endothelial cells, whether it affects VSMC Na(+),K(+)-ATPase activity and whether human SIK1 (hSIK1) represents a potential candidate for blood pressure regulation.METHODS:Localization of SIK1 was performed using immunohistochemistry, mRNA and western blot. Functional assays (Na(+),K(+)-ATPase activity) were performed in VSMCs derived from rat aorta. Genotype-phenotype association studies were performed in three Swedish and one Japanese population-based cohorts.RESULTS:SIK1 was localized in human VSMCs and endothelial cells, as well as a cell line derived from rat aorta. A nonsynonymous single nucleotide polymorphism in the hSIK1 gene exon 3 (C→T, rs3746951) results in the amino acid change (15)Gly→Ser in the SIK1 protein. SIK1-(15)Ser was found to increase plasma membrane Na(+),K(+)-ATPase activity in cultured VSMC line from rat aorta. Genotype-phenotype association studies in three Swedish and one Japanese population-based cohorts suggested that T allele (coding for (15)Ser) was associated with lower blood pressure (P = 0.005 for SBP and P = 0.002 for DBP) and with a decrease in left ventricular mass (P = 0.048).CONCLUSION:The hSIK1 appears to be of potential relevance within VSMC function and blood pressure regulation.
DOI 10.1097/HJH.0b013e32834d3d55
PMID 22045124