the dynamin chemical inhibitor dynasore impairs cholesterol trafficking and sterol-sensitive genes transcription in human hela cells and macrophagesdynamin化学抑制剂dynasore有害胆固醇贩运和sterol-sensitive基因转录在人类的海拉细胞和巨噬细胞.pdf

The Dynamin Chemical Inhibitor Dynasore Impairs Cholesterol Trafficking and Sterol-Sensitive Genes Transcription in Human HeLa Cells and Macrophages 1,2 1,2 1,2 1 3,4 Emmanuelle Girard , Jean Louis Paul , Natalie Fournier , Philippe Beaune , Ludger Johannes , 3,4 . ˆ ´ 1. Christophe Lamaze * , Benoıt Vedie ˆ ˆ ´ ´ 1 AP-HP (Assistance Publique – Hopitaux de Paris), Hopital Europeen Georges Pompidou, Service de Biochimie, Paris, France, 2 Universite Paris-Sud, EA 4529, UFR de ˆ Pharmacie, Chatenay-Malabry, France, 3 CNRS UMR144, Paris, France, 4 Institut Curie, Centre de Recherche, Laboratoire Trafic, Signalisation et Ciblage Intracellulaires, Paris, France Abstract Intracellular transport of cholesterol contributes to the regulation of cellular cholesterol homeostasis by mechanisms that are yet poorly defined. In this study, we characterized the impact of dynasore, a recently described drug that specifically inhibits the enzymatic activity of dynamin, a GTPase regulating receptor endocytosis and cholesterol trafficking. Dynasore strongly inhibited the uptake of low-density lipoprotein (LDL) in HeLa cells, and to a lower extent in human macrophages. In both cell types, dynasore treatment led to the abnormal accumulation of LDL and free cholesterol (FC) within the endolysosomal network. The measure of cholesterol esters (CE) further showed that the delivery of regulatory cholesterol to the endoplasmic reticulum (ER) was