title: Salt-inducible kinase 1 influences Na(+),K(+)-ATPase activity in vascular smooth muscle cells and associates with variations in blood pressure.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  The hSIK1 appears to be of potential relevance within VSMC function and blood pressure regulation.
authors: Membrane Signaling Networks, CMM, Karolinska University Hospital-Solna, Stockholm, Sweden.
authors: Sergej
authors: S
authors: Popov
authors: Angela
authors: A
authors: Silveira
authors: Dick
authors: D
authors: Wågsäter
authors: Hiroshi
authors: H
authors: Takemori
authors: Ryousuke
authors: R
authors: Oguro
authors: Sachiko
authors: S
authors: Matsumoto
authors: Ken
authors: K
authors: Sugimoto
authors: Kei
authors: K
authors: Kamide
authors: Takuo
authors: T
authors: Hirose
authors: Michihiro
authors: M
authors: Satoh
authors: Hirohito
authors: H
authors: Metoki
authors: Masahiro
authors: M
authors: Kikuya
authors: Takayoshi
authors: T
authors: Ohkubo
authors: Tomohiro
authors: T
authors: Katsuya
authors: Hiromi
authors: H
authors: Rakugi
authors: Yutaka
authors: Y
authors: Imai
authors: Fabio
authors: F
authors: Sanchez
authors: Margret
authors: M
authors: Leosdottir
authors: Ann-Christine
authors: AC
authors: Syvänen
authors: Anders
authors: A
authors: Hamsten
authors: Olle
authors: O
authors: Melander
authors: Alejandro M
authors: AM
authors: Bertorello
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000201:enzymology / Q000473:pathology; D001794:Blood Pressure / Q000502:physiology*; D002460:Cell Line; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology*; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000201:enzymology / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000201:enzymology*; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D017346:Protein Serine-Threonine Kinases; C509080:SIK1 protein, human; D000254:Sodium-Potassium-Exchanging ATPase