【作者】 胡清华；

【Author】 Qinghua Hu;Department of Pathophysiology and Key Laboratory of Pulmonary Diseases of Ministry of Health of China,Tongji Medical College,Huazhong Science and Technology University(HUST);

【机构】 华中科技大学同济医学院；

【摘要】 Very recent studies hold promise to reveal the role of stromal interaction molecule 1(STIM1)in non-store-operated Ca2+ entry.Here we showed that in contrast to cytoplasmic membrane redistribution as previously noted,human umbilical vein endothelial STIM1 with a T-to-C nucleotide transition resulting in an amino acid substitution of leucine by proline in the signal peptide sequence translocated to perinuclear membrane upon intracellular Ca2+ depletion,amplified nucleoplasmic Ca2+ signaling through ryanodine receptors-dependent pathway,enhanced the subsequent cAMP responsive element binding protein activity,matrix metalloproteinase-2(MMP-2) gene expression and endothelial tube forming.The abundance of mutated STIM1 and MMP-2 expression were higher in native human umbilical vein endothelial cells of patients with gestational hypertension than controls and were significantly correlated with blood pressure.These findings broaden our understanding about structure-function bias of STIM1 and offer unique insights into its application in nucleoplasmic Ca2+,MMP-2 expression,endothelial dysfunction and pathohysiological mechanism(s) of gestational hypertension.更多还原

【Abstract】 Very recent studies hold promise to reveal the role of stromal interaction molecule 1(STIM1)in non-store-operated Ca2+ entry.Here we showed that in contrast to cytoplasmic membrane redistribution as previously noted,human umbilical vein endothelial STIM1 with a T-to-C nucleotide transition resulting in an amino acid substitution of leucine by proline in the signal peptide sequence translocated to perinuclear membrane upon intracellular Ca2+ depletion,amplified nucleoplasmic Ca2+ signaling through ryanodine receptors-dependent pathway,enhanced the subsequent cAMP responsive element binding protein activity,matrix metalloproteinase-2(MMP-2) gene expression and endothelial tube forming.The abundance of mutated STIM1 and MMP-2 expression were higher in native human umbilical vein endothelial cells of patients with gestational hypertension than controls and were significantly correlated with blood pressure.These findings broaden our understanding about structure-function bias of STIM1 and offer unique insights into its application in nucleoplasmic Ca2+,MMP-2 expression,endothelial dysfunction and pathohysiological mechanism(s) of gestational hypertension.更多还原