Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Salt-inducible kinase 1 influences Na+,K+-ATPase activity in vascular smooth muscle cells and associates with variations in blood pressure.

Popov, Sergej ; Silveira, Angela ; Wågsäter, Dick ; Takemori, Hiroshi ; Oguro, Ryousuke ; Matsumoto, Sachiko ; Sugimoto, Ken ; Kamide, Kei ; Hirose, Takuo and Satoh, Michihiro , et al. (2011) In Journal of Hypertension 29(12). p.2395-2403
Abstract
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... (More)
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 Gly→Ser in the SIK1 protein. SIK1-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 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. (Less)
Please use this url to cite or link to this publication:
@article{e2bca18c-5728-4aad-9e2f-7b1bba90042d,
  abstract     = {{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 Gly→Ser in the SIK1 protein. SIK1-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 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.}},
  author       = {{Popov, Sergej and Silveira, Angela and Wågsäter, Dick and Takemori, Hiroshi and Oguro, Ryousuke and Matsumoto, Sachiko and Sugimoto, Ken and Kamide, Kei and Hirose, Takuo and Satoh, Michihiro and Metoki, Hirohito and Kikuya, Masahiro and Ohkubo, Takayoshi and Katsuya, Tomohiro and Rakugi, Hiromi and Imai, Yutaka and Sanchez, Fabio and Leosdottir, Margrét and Syvänen, Ann-Christine and Hamsten, Anders and Melander, Olle and Bertorello, Alejandro M}},
  issn         = {{1473-5598}},
  language     = {{eng}},
  number       = {{12}},
  pages        = {{2395--2403}},
  publisher    = {{Lippincott Williams & Wilkins}},
  series       = {{Journal of Hypertension}},
  title        = {{Salt-inducible kinase 1 influences Na+,K+-ATPase activity in vascular smooth muscle cells and associates with variations in blood pressure.}},
  url          = {{http://dx.doi.org/10.1097/HJH.0b013e32834d3d55}},
  doi          = {{10.1097/HJH.0b013e32834d3d55}},
  volume       = {{29}},
  year         = {{2011}},
}