首页> 外文期刊>Cell biology international. >The human megakaryocytic cell line UT-7/TPO expresses functional platelet agonist signals mediated through GPVI and thromboxane receptor.
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The human megakaryocytic cell line UT-7/TPO expresses functional platelet agonist signals mediated through GPVI and thromboxane receptor.

机译:人巨核细胞系UT-7 / TPO表达通过GPVI和血栓烷受体介导的功能性血小板激动剂信号。

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We have demonstrated that a unique megakaryocytic cell line UT-7/TPO could respond to one of the primary platelet signals through GP (glycoprotein) VI and a secondary signal of the AA (arachidonic acid) cascade. Unlike other megakaryocytic cell lines, UT-7/TPO was found to express GPVI and its associate signal molecule of FcRgamma (Fc receptor gamma chain). When UT-7/TPO was stimulated with the GPVI agonist convulxin, the [Ca2+]i (intracellular Ca2+) was elevated in a convulxin concentration-dependent manner, and [Ca2+]i elevation was blocked by pretreatment with the Src family kinase inhibitor PP2 and the phospholipase inhibitor U73122. These results strongly indicate that endogenously expressed GPVI signal molecules are functional in UT-7/TPO. Concerning the AA cascade, the expression of COX (cyclooxygenase)-1 and TX (thromboxane) synthase was observed, and this cell line was able to produce TX by exogenous AA, followed by [Ca2+]i elevation mediated through the TX receptor. It is worth noting that convulxin stimulation did not cause TX generation, even through the GPVI pathway and the AA cascade are functional in this cell line. As there are many reports that convulxin-stimulated platelets failed to produce TX, it is suggested that UT-7/TPO has the same property as the platelets in regards to convulxin stimulation. Thus, UT-7/TPO is useful for the observation of both the GPVI pathway and AA cascade without requiring either the induction of differentiation or GPVI transfection. Furthermore, this cell line provides a new tool for research on platelet activation signals.
机译:我们已经证明,独特的巨核细胞系UT-7 / TPO可以通过GP(糖蛋白)VI响应一级血小板信号和AA(花生四烯酸)级联的次级信号。与其他巨核细胞系不同,UT-7 / TPO被发现表达GPVI及其相关信号分子FcRgamma(Fc受体γ链)。当GPVI激动剂惊厥毒素刺激UT-7 / TPO时,[Ca2 +] i(细胞内Ca2 +)以惊厥毒素浓度依赖性的方式升高,并且通过Src家族激酶抑制剂PP2预处理阻止了[Ca2 +] i的升高。和磷脂酶抑制剂U73122。这些结果强烈表明内源表达的GPVI信号分子在UT-7 / TPO中具有功能。关于AA级联,观察到COX(环氧合酶)-1和TX(血栓烷)合酶的表达,并且该细胞系能够通过外源AA产生TX,然后通过TX受体介导的[Ca2 +] i升高。值得注意的是,即使通过GPVI途径和AA级联在此细胞系中起作用,惊厥毒素刺激也不会引起TX产生。由于有许多报道说惊厥刺激的血小板不能产生TX,因此在刺激惊厥方面,UT-7 / TPO与血小板具有相同的性质。因此,UT-7 / TPO可用于观察GPVI途径和AA级联反应,而无需诱导分化或GPVI转染。此外,该细胞系为研究血小板活化信号提供了新的工具。

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