This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, L. Articles by Pownall, H. J. Search for Related Content PubMed PubMed Citation Articles by Li, L. Articles by Pownall, H. J. Related Collections Lipid and lipoprotein metabolism Cell biology/structural biology Cell signalling/signal transduction

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:2636.)
© 2000 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Regulation of Acyl-Coenzyme A:Cholesterol Acyltransferase (ACAT) Synthesis, Degradation, and Translocation by High-Density Lipoprotein₂ at a Low Concentration

Lei Li; Henry J. Pownall

From the Department of Medicine, Baylor College of Medicine, and The Methodist Hospital, Houston, Tex.

Correspondence to Henry J. Pownall, PhD, Department of Medicine, Baylor College of Medicine, MS A-601, 6565 Fannin St, Houston, TX 77030. E-mail hpownall{at}bcm.tmc.edu

Abstract—Although plasma HDL₂ cholesterol concentration stands in inverse relation to risk for atherosclerotic disease, little is known about the mechanism of the apparent cardioprotection. In mouse P388D1 macrophages, HDL₂ at a low concentration (40 µg/mL) inhibits macrophage acyl-coenzyme A:cholesterol acyltransferase (ACAT), the enzyme that catalyzes esterification of intracellular cholesterol. The effects of HDL₂ on ACAT synthesis, degradation, and intracellular translocation were investigated in mouse P388D1 macrophages. HDL₂ at a low concentration enhanced ACAT synthesis but not total ACAT mass. Immunocytochemical studies showed that in the absence of lipoproteins, ACAT associated primarily with the perinuclear region of the cell. The addition of HDL₂, however, induced the transfer of ACAT to vesicular structures and the cell periphery adjacent to the plasma membrane. Subfractionation combined with immunoprecipitation complemented these observations and showed that HDL₂ promoted the transfer of ACAT to the plasma membrane fraction. Brefeldin A, which inhibits vesicular protein transport from the endoplasmic reticulum to the Golgi compartment in mammalian cells, blocked ACAT translocation and partially restored ACAT activity. These results suggest that HDL₂ is an initiating factor in a signal transduction pathway that leads to intracellular ACAT translocation and inactivation.

Key Words: macrophage • lipid metabolism • cholesteryl ester • vesicular transport • ACAT

This article has been cited by other articles:

				A. Larbi, N. Douziech, G. Dupuis, A. Khalil, H. Pelletier, K.-P. Guerard, and T. Fulop Jr Age-associated alterations in the recruitment of signal-transduction proteins to lipid rafts in human T lymphocytes J. Leukoc. Biol., February 1, 2004; 75(2): 373 - 381. [Abstract] [Full Text] [PDF]