阿拉巴马大学的研究人员Irshad H. Chaudry辨认出可以减少受伤和出血后造成肝脏损伤的雌性激素受体路径。
这项研究标题为「G protein-coupled receptor 30-dependent protein kinase A pathway is critical in nongenomic effects of estrogen in attenuating liver injury after trauma-hemorrhage」，发表于4月号的The American Journal of Pathology中。
该研究指出，雌性激素可以改善主体受伤后的反应，但是相关的细胞路径仍然未知。雌性激素可经由二种方式引导细胞过程：与DNA产生交互作用而制造新的蛋白质，或与细胞表面受体结合，产生迅速的蛋白质信号。
这项研究将焦点放在可改善肝脏损伤的细胞表面受体，研究人员利用肝脏损伤及出血的大鼠模型进行这项研究。他们利用一种无法进入细胞中的雌性激素研究这个细胞表面的受体路径。
依照研究人员的预期，发生创伤性出血的大鼠，体内释放了大量的与肝脏受损有关的肝脏酵素。但是，表面雌性激素的治疗减少释放的酵素量。雌性激素处理后，也维持了具有细胞防护效果之Bcl-2和活化的蛋白激酶A之正常含量。
研究人员审查了二种可能与此有关的受体，包括G蛋白质结合受体30 (GPR30)及雌性激素受体阿尔法，以了解它们在调控雌性激素的防护作用中，所扮演的角色。
研究发现抑制雌性激素受体阿尔法对于细胞并无影响，但是细胞表面的GPR30如果不表现，将会减少Bcl-2 和和活化的蛋白激酶A的表现。
这个蛋白质路径的发现，将有助于研究人员发展出治疗受伤患者的新方法。
(资料来源 : biocompare)
原始出处: http://news.biocompare.com/newsstory.asp?id=176744
部分英文原文：
(American Journal of Pathology. 2007;170:1210-1218.)
© 2007 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2007.060883
G Protein-Coupled Receptor 30-Dependent Protein Kinase A Pathway Is Critical in Nongenomic Effects of Estrogen in Attenuating Liver Injury after Trauma-Hemorrhage
Ya-Ching Hsieh, Huang-Ping Yu, Michael Frink, Takao Suzuki, Mashkoor A. Choudhry, Martin G. Schwacha and Irshad H. Chaudry
From the Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama
Although nongenomic effects of 17ß-estradiol (E2) are mediated via the estrogen receptor (ER-), the existence of another novel ER, G protein-coupled receptor 30 (GPR30), has been suggested as a candidate for triggering a broad range of E2-mediated signaling. GPR30 also acts independently of the ER to promote activation of the protein kinase A (PKA) pathway, which protects cells from apoptosis through Bcl-2. In this study, we examined whether the salutary effects of E2 in attenuating hepatic injury after trauma-hemorrhage are mediated via GPR30- or ER--regulated activation of PKA-dependent signaling. At 2 hours after trauma-hemorrhage, administration of E2-conjugated to bovine serum albumin (E2-BSA, membrane impermeable) or E2 induced the up-regulation of ER- and GPR30 and attenuated hepatic injury. This was accompanied by increases in PKA activity and Bcl-2 expression. Inhibition of PKA in E2-BSA-treated trauma-hemorrhage rats by PKA inhibitor H89 prevented the E2-BSA attenuation of hepatic injury. Isolated hepatocytes were transfected with small interfering RNA to suppress GPR30 or ER. We found that suppression of GPR30 but not ER- prevented E2-BSA- or E2-induced PKA activation and Bcl-2 expression. These results suggest that the nongenomic salutary effect of E2 in reducing hepatic injury after trauma-hemorrhage is mediated through the PKA-dependent pathway via GPR30 but not ER-.
