Cultured human astrocytes secrete large cholesteryl ester- andtriglyceride-rich lipoproteins along with endothelial lipase

Yang, Lin ; Liu, Yanzhu ; Forte, Trudy M. ; Chisholm, Jeffrey W. ; Parks, John S. ; Shachter, Neil S.

Lawrence Berkeley National Laboratory

关键词: Lipoproteins;    Triglycerides Lipoproteins Vldl Apolipoproteins C Apolipoproteins E Cellculture Astrocytes Human;    Filtration;    Chromatography;    59 Basic Biological Sciences;   

DOI  :  10.2172/886608
RP-ID  :  LBNL--54501
RP-ID  :  DE-AC02-05CH11231
RP-ID  :  886608

美国|英语

来源: UNT Digital Library

【 摘 要 】

We cultured normal human astrocytes and characterized their secreted lipoproteins. Human astrocytes secreted lipoproteins in the size range of plasma VLDL (Peak 1), LDL (Peak 2), HDL (Peak 3) and a smaller peak (Peak 4), as determined by gel filtration chromatography, nondenaturing gradient gel electrophoresis and transmission electron microscopy. Cholesterol enrichment of astrocytes led to a particular increase in Peak 1. Almost all Peak 2, 3 and 4 cholesterol and most Peak 1 cholesterol was esterified (unlike mouse astrocyte lipoproteins, which exhibited similar peaks but where cholesterol was predominantly non-esterified). Triglycerides were present at about 2/3 the level of cholesterol. LCAT was detected along with two of its activators, apolipoprotein (apo) A-IV and apoC-I. ApoA-I and apoA-II mRNA and protein were absent. ApoJ was present equally in all peaks but apoE was present predominantly in peaks 3 and 4. ApoB was not detected. The electron microscopic appearance of Peak 1 lipoproteins suggested partial lipolysis leading to the detection of a heparin-releasable triglyceride lipase consistent with endothelial lipase. The increased neuronal delivery of lipids from large lipoprotein particles, for which apoE4 has greater affinity than does apoE3, may be a mechanism whereby the apoE {var_epsilon}4 allele contributes to neurodegenerative risk.