Caveolae and caveolin-1 mediate endocytosis and transcytosis of oxidized low density lipoprotein in endothelial cells  

作　　者：Shao-wei SUN Xu-yu ZU Qin-hui TUO Lin-xi CHEN Xiao-yong LEI Kai LI Chao-ke TANG Duan-fang LIAO 

机构地区：[1]Province Key Laboratory of Pharmacoprotomics, Institute of Pharmacy and Pharmacology, University of South China, Hengyang 421001, China [2]Department of Traditional Chinese Diagnostics, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China [3]Key Laboratory for Atherosclerology of Hu-nan Province, Life Science Research Center, University of South China, Hengyang 421001, China [4]Molecular Medicine Center and the Second Affiliated Hospital, Suzhou University, Suzhou 215004, China

出　　处：《Acta Pharmacologica Sinica》2010年第10期1336-1342,共7页中国药理学报（英文版）

摘　　要：Aim： To explore the mechanisms involved in ox-LDL transcytosis across endothelial cells and the role of caveolae in this process. Methods： An in vitro model was established to investigate the passage of oxidized low density lipoprotein （ox-LDL） through a tight monolayer of human umbilical vein endothelial cells （HUVEC） cultured on a collagen-coated filter. Passage of Dil-labeled ox-LDL through the monolayer was measured using a fluorescence spectrophotometer. The uptake and efflux of ox-LDL by HUVEC were determined using fluorescence microscopy and HPLC. Results： Caveolae inhibitors - carrageenan （250 pg/mL）, filipin （5 pg/mL）, and nocodazole （33 pmol/L）-decreased the transport of ox-LDL across the monolayer by 48.9%, 72.4%, and 79.8% as compared to the control group. In addition, they effectively decreased ox-LDL uptake and inhibited the efflux of ox-LDL. Caveolin-1 and LOX-1 were up-regulated by ox-LDL in a time-dependent manner and decreased gradually after depletion of ox-LDL （P〈O.05）. After treatment HUVEC with ox-LDL and silencing caveolin-1, NF-KB transloca- tion to the nucleus was blocked and LOX-1 expression decreased （P〈O.05）. Conclusion： Caveolae can be a carrier for ox-LDL and may be involved in the uptake and transcytosis of ox-LDL by HUVEC.Aim： To explore the mechanisms involved in ox-LDL transcytosis across endothelial cells and the role of caveolae in this process. Methods： An in vitro model was established to investigate the passage of oxidized low density lipoprotein （ox-LDL） through a tight monolayer of human umbilical vein endothelial cells （HUVEC） cultured on a collagen-coated filter. Passage of Dil-labeled ox-LDL through the monolayer was measured using a fluorescence spectrophotometer. The uptake and efflux of ox-LDL by HUVEC were determined using fluorescence microscopy and HPLC. Results： Caveolae inhibitors - carrageenan （250 pg/mL）, filipin （5 pg/mL）, and nocodazole （33 pmol/L）-decreased the transport of ox-LDL across the monolayer by 48.9%, 72.4%, and 79.8% as compared to the control group. In addition, they effectively decreased ox-LDL uptake and inhibited the efflux of ox-LDL. Caveolin-1 and LOX-1 were up-regulated by ox-LDL in a time-dependent manner and decreased gradually after depletion of ox-LDL （P〈O.05）. After treatment HUVEC with ox-LDL and silencing caveolin-1, NF-KB transloca- tion to the nucleus was blocked and LOX-1 expression decreased （P〈O.05）. Conclusion： Caveolae can be a carrier for ox-LDL and may be involved in the uptake and transcytosis of ox-LDL by HUVEC.

关 键 词：CAVEOLAE CAVEOLIN-1 oxidized low density lipoprotein atherosclerosis TRANSCYTOSIS human umbilical vein endothelial cells 

分 类 号：Q513.5[生物学—生物化学] Q463