Journal of Lipid Research, Vol 37, 1556-1568, Copyright © 1996 by Lipid Research, Inc.

ARTICLES

Quantitative analysis of hydrophobic amine inhibition of intracellular cholesterol transport

KW Underwood, B Andemariam, GL McWilliams and L Liscum
Department of Physiology, Tufts University School of Medicine, Boston, MA 02111, USA.

U18666A and imipramine are hydrophobic amines that inhibit intracellular cholesterol transport pathways. In this study, we conducted dose-response curves for each of the cholesterol transport pathways. Our analyses indicate that hydrophobic amine inhibition of LDL-stimulated cholesterol esterification is much more sensitive to inhibition than either the combined bulk movement of cholesterol from lysosomes to the plasma membrane and from the plasma membrane to the endoplasmic reticulum. Hydrophobic amines must inhibit a previously uncharacterized pathway from lysosomes to the endoplasmic reticulum or a signaling event that activates acyl CoA:cholesterol acyltransferase. Possible mechanisms for U18666A action were evaluated. The function of p-glycoprotein, which has been implicated in cholesterol transport, was unaffected by U18666A. We have evidence for a specific membrane U18666A binding site, which we hypothesize is involved in the plasma membrane to endoplasmic reticulum cholesterol transport pathway. Identification of the binding site and mechanism of hydrophobic amine action may provide information essential for understanding intracellular cholesterol transport.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				T. A. Pagler, A. Neuhofer, H. Laggner, W. Strobl, and H. Stangl Cholesterol efflux via HDL resecretion occurs when cholesterol transport out of the lysosome is impaired J. Lipid Res., October 1, 2007; 48(10): 2141 - 2150. [Abstract] [Full Text] [PDF]

				I. Delton-Vandenbroucke, J. Bouvier, A. Makino, N. Besson, J.-F. Pageaux, M. Lagarde, and T. Kobayashi Anti-bis(monoacylglycero)phosphate antibody accumulates acetylated LDL-derived cholesterol in cultured macrophages J. Lipid Res., March 1, 2007; 48(3): 543 - 552. [Abstract] [Full Text] [PDF]

				E. Ikonen Mechanisms for cellular cholesterol transport: defects and human disease. Physiol Rev, October 1, 2006; 86(4): 1237 - 1261. [Abstract] [Full Text] [PDF]

				G. Chinetti-Gbaguidi, E. Rigamonti, L. Helin, A. L. Mutka, M. Lepore, J. C. Fruchart, V. Clavey, E. Ikonen, S. Lestavel, and B. Staels Peroxisome proliferator-activated receptor {alpha} controls cellular cholesterol trafficking in macrophages J. Lipid Res., December 1, 2005; 46(12): 2717 - 2725. [Abstract] [Full Text] [PDF]

				J. Qian, S. Morley, K. Wilson, P. Nava, J. Atkinson, and D. Manor Intracellular trafficking of vitamin E in hepatocytes: the role of tocopherol transfer protein J. Lipid Res., October 1, 2005; 46(10): 2072 - 2082. [Abstract] [Full Text] [PDF]

				E. Rigamonti, L. Helin, S. Lestavel, A.L. Mutka, M. Lepore, C. Fontaine, M.A. Bouhlel, S. Bultel, J.C. Fruchart, E. Ikonen, et al. Liver X Receptor Activation Controls Intracellular Cholesterol Trafficking and Esterification in Human Macrophages Circ. Res., September 30, 2005; 97(7): 682 - 689. [Abstract] [Full Text] [PDF]

				N. E. Freeman, A. E. Rusinol, M. Linton, D. L. Hachey, S. Fazio, M. S. Sinensky, and D. Thewke Acyl-coenzyme A:cholesterol acyltransferase promotes oxidized LDL/oxysterol-induced apoptosis in macrophages J. Lipid Res., September 1, 2005; 46(9): 1933 - 1943. [Abstract] [Full Text] [PDF]

				S. C.D. van IJzendoorn, J. M. van der Wouden, G. Liebisch, G. Schmitz, and D. Hoekstra Polarized Membrane Traffic and Cell Polarity Development Is Dependent on Dihydroceramide Synthase-Regulated Sphinganine Turnover Mol. Biol. Cell, September 1, 2004; 15(9): 4115 - 4124. [Abstract] [Full Text] [PDF]

				R. E. Soccio and J. L. Breslow Intracellular Cholesterol Transport Arterioscler. Thromb. Vasc. Biol., July 1, 2004; 24(7): 1150 - 1160. [Abstract] [Full Text] [PDF]

				J. Zhang, N. Dudley-Rucker, J. R. Crowley, E. Lopez-Perez, M. Issandou, J. E. Schaffer, and D. S. Ory The steroidal analog GW707 activates the SREBP pathway through disruption of intracellular cholesterol trafficking J. Lipid Res., February 1, 2004; 45(2): 223 - 231. [Abstract] [Full Text] [PDF]

				C. M. Adams, J. L. Goldstein, and M. S. Brown Cholesterol-induced conformational change in SCAP enhanced by Insig proteins and mimicked by cationic amphiphiles PNAS, September 16, 2003; 100(19): 10647 - 10652. [Abstract] [Full Text] [PDF]

				R. A. Carabeo, D. J. Mead, and T. Hackstadt Golgi-dependent transport of cholesterol to the Chlamydia trachomatis inclusion PNAS, May 27, 2003; 100(11): 6771 - 6776. [Abstract] [Full Text] [PDF]

				B. Feng and I. Tabas ABCA1-mediated Cholesterol Efflux Is Defective in Free Cholesterol-loaded Macrophages. MECHANISM INVOLVES ENHANCED ABCA1 DEGRADATION IN A PROCESS REQUIRING FULL NPC1 ACTIVITY J. Biol. Chem., November 1, 2002; 277(45): 43271 - 43280. [Abstract] [Full Text] [PDF]

				L. Liscum, E. Arnio, M. Anthony, A. Howley, S. L. Sturley, and M. Agler Identification of a pharmaceutical compound that partially corrects the Niemann-Pick C phenotype in cultured cells J. Lipid Res., October 1, 2002; 43(10): 1708 - 1717. [Abstract] [Full Text] [PDF]

				N. D. Ridgway, T. A. Lagace, H. W. Cook, and D. M. Byers Differential Effects of Sphingomyelin Hydrolysis and Cholesterol Transport on Oxysterol-binding Protein Phosphorylation and Golgi Localization J. Biol. Chem., November 20, 1998; 273(47): 31621 - 31628. [Abstract] [Full Text] [PDF]

				K. W. Underwood, N. L. Jacobs, A. Howley, and L. Liscum Evidence for a Cholesterol Transport Pathway from Lysosomes to Endoplasmic Reticulum That Is Independent of the Plasma Membrane J. Biol. Chem., February 13, 1998; 273(7): 4266 - 4274. [Abstract] [Full Text] [PDF]

				Y. Lange, J. Ye, and J. Chin The Fate of Cholesterol Exiting Lysosomes J. Biol. Chem., July 4, 1997; 272(27): 17018 - 17022. [Abstract] [Full Text] [PDF]

				C. L. Baum, E. J. Reschly, A. K. Gayen, M. E. Groh, and K. Schadick Sterol Carrier Protein-2 Overexpression Enhances Sterol Cycling and Inhibits Cholesterol Ester Synthesis and High Density Lipoprotein Cholesterol Secretion J. Biol. Chem., March 7, 1997; 272(10): 6490 - 6498. [Abstract] [Full Text] [PDF]