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Sphingosine 1-phosphate receptors mediate stimulatory and inhibitory signalings for expression of adhesion molecules in endothelial cells

机译:1-磷酸鞘氨醇受体介导内皮细胞中粘附分子表达的刺激和抑制信号

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Sphingosine l-phosphate (SlP) stimulates expression of vascular cell adhesion molecule-1 and intercellular adhesion rnolecule-1 in human umbilical vein endothelial cells. SlP-induced actions were associated with nuclear factor kappa-B activation and inhibited by pertussis toxin as well as by antisense oligonucleotides specific to SlP receptors, especially, SlP(3). SlP also stimulated endothelial nitric oxide synthase (eNOS) and its activation was markedly inhibited by the antisense oligonucleotide for the SlP, receptor rather than that for the SlP3 receptor. The dose-response curve of SlP to stimulate adhesion molecule expression was shifted to the left in the presence of the phosphatidylinositol 3-kinase inhibitor wortmannin and the NOS inhibitor N omega-nitro-L-arginine methyl ester. NO donor S-nitroso-N-acetylpenicillamine inhibited SIP-induced adhesion molecule expression. Moreover, tumor necrosis factor-alpha-induced adhesion molecule expression was markedly inhibited by SlP in a manner sensitive to inhibitors for PI3-K and NOS. These results suggest that SlP receptors are coupled to both stimulatory and inhibitory pathways for adhesion molecule expression. The stimulatory pathway involves nuclear factor kappa-B and inhibitory one does phosphatidylinositol 3-kinase and NOS. (c) 2005 Elsevier Inc. All rights reserved.
机译:磷酸鞘氨醇(SlP)刺激人脐静脉内皮细胞中血管细胞粘附分子1和细胞间粘附核酸1的表达。 S1P诱导的作用与核因子κB激活有关,并被百日咳毒素以及对S1P受体,特别是SlP(3)特异的反义寡核苷酸抑制。 S1P还刺激内皮一氧化氮合酶(eNOS),并且其激活被S1P受体的反义寡核苷酸而不是S1P3受体的反义寡核苷酸显着抑制。在磷脂酰肌醇3-激酶抑制剂渥曼青霉素和NOS抑制剂Nω-硝基-L-精氨酸甲酯的存在下,S1P刺激粘附分子表达的剂量反应曲线向左移动。 NO供体S-亚硝基-N-乙酰青霉胺抑制SIP诱导的粘附分子表达。而且,S1P以对PI3-K和NOS抑制剂敏感的方式显着抑制了肿瘤坏死因子-α诱导的粘附分子表达。这些结果表明,S1P受体与粘附分子表达的刺激途径和抑制途径都偶联。刺激途径涉及核因子κB,而抑制途径涉及磷脂酰肌醇3-激酶和NOS。 (c)2005 Elsevier Inc.保留所有权利。

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