According to a genome-wide association study,intronic SNPs within the human sterile 20/SPS1-related proline/alanine-rich kinase(SPAK) gene was linked to 20% of the general population and may be associated with elevate...According to a genome-wide association study,intronic SNPs within the human sterile 20/SPS1-related proline/alanine-rich kinase(SPAK) gene was linked to 20% of the general population and may be associated with elevated blood pressure. As cell volume changes,mammalian SPAK kinases respond to phosphorylate and regulate cation-coupled chloride co-transporter activity. To our knowledge,phosphorylation of upstream with-no-lysine(K)(WNK) kinases would activate SPAK kinases. The activation of WNK-OSR1/SPAK cascade on the kidneys and aortic tissue is related to the development of hypertension. Several regulators of the WNK pathway such as the Kelch kinase protein 3-Cullin 3 E3 ligase,hyperinsulinemia,and low potassium intake to mediate hypertension have been identified. In addition,the SPAK kinases may affect the action of renin-angiotensin-aldosterone system on blood pressure as well. In 2010,two SPAK knock-in and knock-out mouse models have clarified the pathogenesis of lowering blood pressure by influencing the receptors on the kidneys and aortic smooth muscle. More recently,two novel SPAK inhibitors for mice,Stock 1S-14279 and Closantel were discovered in 2014. Targeting of SPAK seems to be promising for future antihypertensive therapy. Therefore we raised some viewpoints for the issue for the antihypertensive therapy on the SPAK(gene or kinase).展开更多
目的:探讨乳源活性肽β-酪啡肽-7(β-Casomorphin-7,β-CM7)应用于食品时对葡萄糖吸收的影响及其作用机制.方法:选用健康成年SD大鼠,分为对照组(0mol/Lβ-CM7),L低剂量组、M中剂量组、H高剂量组(终浓度分别为7.5×10-7,7.5×10-...目的:探讨乳源活性肽β-酪啡肽-7(β-Casomorphin-7,β-CM7)应用于食品时对葡萄糖吸收的影响及其作用机制.方法:选用健康成年SD大鼠,分为对照组(0mol/Lβ-CM7),L低剂量组、M中剂量组、H高剂量组(终浓度分别为7.5×10-7,7.5×10-6,7.5×10-5mol/L).利用翻转离体小肠囊模型进行实验:(1)葡萄糖氧化酶法测定翻转后小肠内液葡萄糖含量;(2)比色法测定小肠黏膜Na+-K+-ATP酶活力;(3)荧光定量PCR法分析小肠黏膜组织中钠葡萄糖共转运载体(SGLT-1)和葡萄糖协助扩散转运载体(GLUT-2) mRNA的表达.结果:在离体环境下β-CM7在7.5×10-7-7.5×10-5mol/L浓度下对葡萄糖的吸收均有一定的抑制作用(1.09mol/L,1.24mol/L,1.12mol/L vs 1.74mol/L,P=0.01,0.04,0.02),能够降低Na+-K+-ATP酶活力(85.73,112.06,109.68 vs 114.93,P=0.004,0.73,0.54);荧光定量PCR结果发现:与对照组相比,β-CM7能够显著降低SGLT-1及GLUT-2 mRNA水平(0.46,0.58,0.77 vs 1.11,P=0.20,0.05,0.02;0.50,0.66,0.85 vs 1.14,P=0.30,0.14,0.03).结论:β-CM7可以通过降低Na+-K+-ATP酶活力及下调SGLT-1、GLUT-2 mRNA水平,减少大鼠小肠对葡萄糖的吸收.展开更多
文摘According to a genome-wide association study,intronic SNPs within the human sterile 20/SPS1-related proline/alanine-rich kinase(SPAK) gene was linked to 20% of the general population and may be associated with elevated blood pressure. As cell volume changes,mammalian SPAK kinases respond to phosphorylate and regulate cation-coupled chloride co-transporter activity. To our knowledge,phosphorylation of upstream with-no-lysine(K)(WNK) kinases would activate SPAK kinases. The activation of WNK-OSR1/SPAK cascade on the kidneys and aortic tissue is related to the development of hypertension. Several regulators of the WNK pathway such as the Kelch kinase protein 3-Cullin 3 E3 ligase,hyperinsulinemia,and low potassium intake to mediate hypertension have been identified. In addition,the SPAK kinases may affect the action of renin-angiotensin-aldosterone system on blood pressure as well. In 2010,two SPAK knock-in and knock-out mouse models have clarified the pathogenesis of lowering blood pressure by influencing the receptors on the kidneys and aortic smooth muscle. More recently,two novel SPAK inhibitors for mice,Stock 1S-14279 and Closantel were discovered in 2014. Targeting of SPAK seems to be promising for future antihypertensive therapy. Therefore we raised some viewpoints for the issue for the antihypertensive therapy on the SPAK(gene or kinase).
文摘目的:探讨乳源活性肽β-酪啡肽-7(β-Casomorphin-7,β-CM7)应用于食品时对葡萄糖吸收的影响及其作用机制.方法:选用健康成年SD大鼠,分为对照组(0mol/Lβ-CM7),L低剂量组、M中剂量组、H高剂量组(终浓度分别为7.5×10-7,7.5×10-6,7.5×10-5mol/L).利用翻转离体小肠囊模型进行实验:(1)葡萄糖氧化酶法测定翻转后小肠内液葡萄糖含量;(2)比色法测定小肠黏膜Na+-K+-ATP酶活力;(3)荧光定量PCR法分析小肠黏膜组织中钠葡萄糖共转运载体(SGLT-1)和葡萄糖协助扩散转运载体(GLUT-2) mRNA的表达.结果:在离体环境下β-CM7在7.5×10-7-7.5×10-5mol/L浓度下对葡萄糖的吸收均有一定的抑制作用(1.09mol/L,1.24mol/L,1.12mol/L vs 1.74mol/L,P=0.01,0.04,0.02),能够降低Na+-K+-ATP酶活力(85.73,112.06,109.68 vs 114.93,P=0.004,0.73,0.54);荧光定量PCR结果发现:与对照组相比,β-CM7能够显著降低SGLT-1及GLUT-2 mRNA水平(0.46,0.58,0.77 vs 1.11,P=0.20,0.05,0.02;0.50,0.66,0.85 vs 1.14,P=0.30,0.14,0.03).结论:β-CM7可以通过降低Na+-K+-ATP酶活力及下调SGLT-1、GLUT-2 mRNA水平,减少大鼠小肠对葡萄糖的吸收.
