阿拉巴馬大學的研究人員Irshad H. Chaudry辨認出可以減少受傷和出血后造成肝臟損傷的雌性激素受體路徑,。
這項研究標題為「G protein-coupled receptor 30-dependent protein kinase A pathway is critical in nongenomic effects of estrogen in attenuating liver injury after trauma-hemorrhage」，發(fā)表于4月號的The American Journal of Pathology中,。
該研究指出,，雌性激素可以改善主體受傷后的反應，但是相關的細胞路徑仍然未知,。雌性激素可經由二種方式引導細胞過程：與DNA產生交互作用而制造新的蛋白質,，或與細胞表面受體結合，產生迅速的蛋白質信號,。
這項研究將焦點放在可改善肝臟損傷的細胞表面受體,，研究人員利用肝臟損傷及出血的大鼠模型進行這項研究。他們利用一種無法進入細胞中的雌性激素研究這個細胞表面的受體路徑,。
依照研究人員的預期,，發(fā)生創(chuàng)傷性出血的大鼠，體內釋放了大量的與肝臟受損有關的肝臟酵素,。但是,，表面雌性激素的治療減少釋放的酵素量,。雌性激素處理后,，也維持了具有細胞防護效果之Bcl-2和活化的蛋白激酶A之正常含量。
研究人員審查了二種可能與此有關的受體,，包括G蛋白質結合受體30 (GPR30)及雌性激素受體阿爾法,，以了解它們在調控雌性激素的防護作用中，所扮演的角色,。
研究發(fā)現抑制雌性激素受體阿爾法對于細胞并無影響,，但是細胞表面的GPR30如果不表現，將會減少Bcl-2 和和活化的蛋白激酶A的表現,。
這個蛋白質路徑的發(fā)現,，將有助于研究人員發(fā)展出治療受傷患者的新方法。
(資料來源 : biocompare)
原始出處: 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-.
