Regulation of LPA receptor function by estrogens
Regulation of LPA receptor function by estrogens
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DOI：
10.1016/j.bbamcr.2007.11.014
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发表时间：
2008-02-01
影响因子：
5.1
通讯作者：
Adolfo Garcia-Sainz, J.
中科院分区：
文献类型：
--
作者：
Gonzalez-Arenas, Aliesha;Avendano-Vazquez, S. Erendira;Adolfo Garcia-Sainz, J.
17β-雌二醇诱导稳定表达LPA(1)受体和瞬时表达雌激素受体α的C9细胞LPA(1)受体脱敏。这种脱敏表现为溶血磷脂酸介导的Ca(2+)动员减少，并与受体磷酸化和内化有关。17β-雌二醇的这些作用迅速(发生在5分钟以上)，并被雌激素受体拮抗剂10 182780阻断。同样，磷脂酰肌醇3-激酶(Wortmannin和LY294002)和蛋白激酶C(Stauroporine和GO 6976)的抑制剂可阻断17β-雌二醇诱导的LPA(1)受体脱敏和磷酸化。共聚焦显微镜显示LPA(1)受体内化对17β-雌二醇处理的反应。免疫共沉淀法表明LPA(1)受体与蛋白激酶Cα之间存在关联。在没有刺激的情况下，蛋白激酶Cα与LPA(1)受体相关，这种关联在17β-雌二醇的反应下以动态的方式进一步增加。结果表明，在C9细胞中，雌激素通过雌激素受体a参与蛋白激酶Cα和磷脂酰肌醇3-激酶参与调节LPA(1)的作用。(C)2007 Elsevier B.V.保留所有权利。
17 beta-Estradiol induced LPA(1) receptor desensitization in C9 cells stably expressing LPA(1) receptors and transiently expressing estrogen receptor alpha. Such desensitization was evidenced by a reduction in lysophosphatidic acid-mediated Ca(2+)mobilization and it was associated to receptor phosphorylation and internalization. These effects of 17 beta-estradiol were rapid (taking place over 5 min) and were blocked by the estrogen receptor antagonist 10 182780. Similarly, inhibitors of phosphoinositide 3-kinase (wortmannin and LY294002) and of protein kinase C (staurosporine and Go 6976) blocked 17 beta-estradiol-induced LPA(1) receptor desensitization and phosphorylation. Confocal microscopy evidenced LPA(1) receptor internalization in response to 17 beta-estradiol treatment. Association between LPA(1) receptors and protein kinase C alpha was suggested by co-immunoprecipitation assays. Protein kinase C alpha was associated with LPA(1) receptors in the absence of stimulus and such association further increased in a dynamic fashion in response to 17 beta-estradiol. The results demonstrated that in C9 cells estrogens modulate LPA(1) action through estrogen receptor a with the participation of protein kinase C alpha and phosphoinositide 3-kinase. (C) 2007 Elsevier B.V. All rights reserved.