期刊
JOURNAL OF LIPID RESEARCH
卷 59, 期 7, 页码 1114-1131出版社
ELSEVIER
DOI: 10.1194/jlr.R083121
关键词
adrenal; liver; bile; steroids
资金
- National Institutes of Health, National Heart, Lung, and Blood Institute [R56HL122773]
- VA Biomedical Laboratory Research and Development Merit Review [2I01BX001923]
- Senior Research Career Scientist (SRCS) Award [IK6BX004200]
- [10BX000398]
Cholesterol is required for maintenance of plasma membrane fluidity and integrity and for many cellular functions. Cellular cholesterol can be obtained from lipoproteins in a selective pathway of HDL-cholesteryl ester (CE) uptake without parallel apolipoprotein uptake. Scavenger receptor B type 1 (SR-B1) is a cell surface HDL receptor that mediates HDL-CE uptake. It is most abundantly expressed in liver, where it provides cholesterol for bile acid synthesis, and in steroidogenic tissues, where it delivers cholesterol needed for storage or steroidogenesis in rodents. SR-B1 transcription is regulated by trophic hormones in the adrenal gland, ovary, and testis; in the liver and elsewhere, SR-B1 is subject to posttranscriptional and posttranslational regulation. SR-B1 operates in several metabolic processes and contributes to pathogenesis of atherosclerosis, inflammation, hepatitis C virus infection, and other conditions. Here, we summarize characteristics of the selective uptake pathway and involvement of microvillar channels as facilitators of selective HDL-CE uptake. We also present the potential mechanisms of SR-B1-mediated selective cholesterol transport; the transcriptional, posttranscriptional, and posttranslational regulation of SR-B1; and the impact of gene variants on expression and function of human SR-B1. A better understanding of this unique pathway and SR-B1's role may yield improved therapies for a wide variety of conditions.
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