教師資料查詢 | 類別: 期刊論文 | 教師: 陳曜鴻 CHEN, YAU-HUNG (瀏覽個人網頁)

標題:Impairment of the Cellular Distribution and Stability of the Erythropoietin Receptor Through the Direct Targeting of Aristolochic Acid
學年103
學期2
出版(發表)日期2015/06/30
作品名稱Impairment of the Cellular Distribution and Stability of the Erythropoietin Receptor Through the Direct Targeting of Aristolochic Acid
作品名稱(其他語言)
著者Chen YH; Chou CY; Sun CY
單位
出版者
著錄名稱、卷期、頁數Toxicological Sciences 147(1), p.246-254
摘要Aristolochic acid (AA) nephropathy is complicated with early onset and severe anemia. The molecular pathological mechanism of AA-induced anemia remains unclear. The aim of this study was to evaluate the putative pathological roles of the erythropoietin receptor (EPOR) in AA-induced anemia in both AA nephropathy zebrafish and cultured human renal tubular cells (HK2). Immunofluorescence staining experiments revealed that AA colocalizes with the EPOR in zebrafish embryos as well as in the cytoplasm of HK2 cells. After exogenous EPO stimulation, the EPOR was detected in the plasma membrane of HK cells. However, cotreatment with AA and EPO inhibited EPOR signaling and its membrane localization upon EPO stimulation. The results of studies with a protein synthesis inhibitor and a lysosome inhibitor revealed that AA accelerates the lysosomal degradation of EPOR. The molecular docking results suggest that AA may interact with the N-terminus of EPOR. Together with the results of light absorption and in vitro competition assays, we concluded that AA treatment impairs EPOR membrane localization, accelerates its lysosomal degradation, and consequently downregulates EPOR signaling by direct targeting. The results of this study may further detail the pathological mechanism of severe anemia complicated with AA nephropathy.
關鍵字anemia;aristolochic acid;erythropoietin receptor;lysosome;molecular docking
語言英文
ISSN1096-6080;1096-0929
期刊性質國外
收錄於SCI;
產學合作
通訊作者
審稿制度
國別英國
公開徵稿
出版型式,電子版,紙本
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