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Ingress and Egress of Cholesterol

  • O. Stein
  • Y. Stein
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)

Abstract

Cholesterol ingress into cells by receptor-mediated uptake of low-density lipoprotein involves the uptake of the entire lipoprotein particle. However, a nonnegligible fraction of LDL catabolism is accounted for by non-receptor-mediated mechanisms, which might also include cellular uptake of lipoprotein components. One example of such a process is the preferential uptake of cholesteryl ester over apoprotein B from chylomicrons, which was studied with the help of its unhydrolyzable ether analogue cholesteryl linoleyl ether (CLE) and was shown to be mediated by lipoprotein lipase (LPL).

In other experiments the uptake of CLE and protein was compared after incubation of rat hepatocytes, rat adrenal cells, and murine macrophages with labeled HDL. In all these cell types there was a higher uptake of [3H]CLE-HDL than [125I]HDL, but the degree of this difference varied among the different cell types.

Egress of free cholesterol from cells was studied in model systems in culture, and it appears that the acceptors of FC in plasma and probably in extracellular fluid are HDL and HDL apoprotein-phospholipid complexes, which in model systems form disklike structures. The occurrence of disks in prenodal peripheral lymph was demonstrated in dogs. These disks were composed predominantly of apolipoproteins A-I and A-IV and phospholipids and had a high free cholesterol to cholesteryl ester ratio. Therefore, the role of apolipoprotein A-IV in FC removal was studied in cultured cells. Liposomes prepared from a nonhydrolyzable ether analogue of phosphatidylcholine and rat apoproteins A-I or A-IV were equally active in FC removal from cells.

Recently, the possibility of egress of cholesteryl ester (CE) from tissues was studied. Accumulation of CE in the aorta during development of atherosclerosis reflects a disbalance between inflow and outflow of cholesterol. Egress of CE could occur by efflux of intact LDL particles or by efflux of CE mediated by cholesteryl ester transfer protein (CETP). This latter possibility was studied in model systems in cell culture designed to simulate conditions in the aortic wall, using [14C]CE and [3H]CLE labeled liposomes or lipoproteins as cholesteryl ester donors. The results obtained showed that CETP isolated from human LPDS enhanced efflux of liposome [3H]CLE and [14C]CE from the interstitium of cultured aortic smooth muscle cells into the culture medium. Efflux of lipoprotein CE from interstitium was also studied using cationized LDL labeled with [3H]CLE, and enhancement of [3H]CLE efflux occurred in the presence of CETP.

Keywords

Cholesteryl Ester Lipoprotein Lipase Cholesteryl Ester Transfer Protein Free Cholesterol Reverse Cholesterol Transport 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • O. Stein
    • 1
    • 2
  • Y. Stein
    • 1
    • 2
  1. 1.Department of Experimental Medicine and Cancer ResearchHebrew University-Hadassah Medical SchoolIsrael
  2. 2.Lipid Research Laboratory, Department of Medicine BHadassah University HospitalEin Karem, JerusalemIsrael

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