Membrane Signaling Networks, CMM, Karolinska University Hospital-Solna, Stockholm, Sweden.
J Hypertens. 2011 Dec;29(12):2395-403. doi: 10.1097/HJH.0b013e32834d3d55.
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.
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.
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).
The hSIK1 appears to be of potential relevance within VSMC function and blood pressure regulation.
原发性高血压是一种复杂的疾病，其病因涉及多种遗传和环境因素，如盐摄入量。盐诱导激酶 1（SIK1）是一种类似于蔗糖非发酵的激酶同工型，属于 AMPK（5' 腺苷单磷酸激活蛋白激酶）家族。SIK1 的活性会因高盐摄入而增加，在调节细胞膜 Na(+)，K(+) -ATP 酶方面发挥着重要作用。本研究的目的是研究 SIK1 是否存在于血管平滑肌细胞（VSMC）和内皮细胞中，它是否影响 VSMC Na(+)，K(+) -ATP 酶的活性，以及人 SIK1（hSIK1）是否代表血压调节的潜在候选物。
通过免疫组织化学、mRNA 和 Western blot 检测 SIK1 的定位。在源自大鼠主动脉的 VSMC 中进行功能测定（Na(+)，K(+) -ATP 酶活性）。在三个瑞典和一个日本基于人群的队列中进行基因型-表型关联研究。
SIK1 定位于人 VSMC 和内皮细胞，以及源自大鼠主动脉的细胞系。hSIK1 基因外显子 3 中的一个非同义单核苷酸多态性（C→T，rs3746951）导致 SIK1 蛋白中的氨基酸变化（15）Gly→Ser。在源自大鼠主动脉的 VSMC 系中发现 SIK1-(15)Ser 增加了质膜 Na(+)，K(+) -ATP 酶的活性。在三个瑞典和一个日本基于人群的队列中的基因型-表型关联研究表明，T 等位基因（编码（15）Ser）与较低的血压（SBP 的 P=0.005 和 DBP 的 P=0.002）和左心室质量降低相关（P=0.048）。
hSIK1 似乎与 VSMC 功能和血压调节有关。
