Modulation of the LDL receptor and LRP levels by HIV protease inhibitors

Journal of Lipid Research

Volumn 44, Issue 10, 2003, Pages 1859-1869

  Tran, Huan ^a   Robinson, Susan ^a   Mikhailenko, Irina ^a   Strickland, Dudley K ^a,b  

^a HOLLAND LABORATORY   (United States)

^b GEORGE WASHINGTON UNIVERSITY SCHOOL OF MEDICINE AND HEALTH SCIENCES   (United States)

Author keywords

Cholesterol; Endoplasmic reticulum stress; Human immunodeficiency virus; Lipids; Low density lipoprotein receptor related protein; Proteolysis; Therapy

Indexed keywords

AMPRENAVIR; CHOLESTEROL; INDINAVIR; LOPINAVIR; LOW DENSITY LIPOPROTEIN RECEPTOR; LOW DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN; NELFINAVIR; PROTEINASE INHIBITOR; RITONAVIR; SAQUINAVIR; STEROL REGULATORY ELEMENT BINDING PROTEIN; STEROL REGULATORY ELEMENT BINDING PROTEIN 1; UNCLASSIFIED DRUG;

ARTICLE; ATHEROGENESIS; CHOLESTEROL BLOOD LEVEL; CONTROLLED STUDY; DRUG MECHANISM; GENE CONTROL; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYPERCHOLESTEROLEMIA; METABOLIC DISORDER; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL;

ANTI-HIV AGENTS; CCAAT-ENHANCER-BINDING PROTEINS; CELLS, CULTURED; CHOLESTEROL; DNA-BINDING PROTEINS; ENDOPLASMIC RETICULUM; HIV PROTEASE INHIBITORS; HUMANS; LIPOPROTEINS; NELFINAVIR; OXIDATIVE STRESS; RECEPTORS, LDL; RNA, MESSENGER; STEROL REGULATORY ELEMENT BINDING PROTEIN 1; TRANSCRIPTION FACTORS;

EID: 0242322487     PISSN: 00222275     EISSN: None     Source Type: Journal    
DOI: 10.1194/jlr.M200487-JLR200     Document Type: Article

References (66)

1. Flexner, C. 2000. Dual protease inhibitor therapy in HIV-infected patients: pharmacologic rationale and clinical benefits. Annu. Rev. Pharmacol. Toxicol. 40: 649-674.
2. Carr, A., K. Samaras, D. J. Chisholm, and D. A. Cooper. 1998. Pathogenesis of HIV-1-protease inhibitor-associated peripheral lipodystrophy, hyperlipidaemia, and insulin resistance. Lancet. 351: 1881-1883.
3. Carr, A., K. Samaras, A. Thorisdottir, G. R. Kaufmann, D. J. Chisholm, and D. A. Cooper. 1999. Diagnosis, prediction, and natural course of HIV-1 protease-inhibitor-associated lipodystrophy, hyperlipidaemia, and diabetes mellitus: a cohort study. Lancet. 353: 2093-2099.
4. Carr, A. 2000. HIV protease inhibitor-related lipodystrophy syndrome. Clin. Infect. Dis. 30 (Suppl. 2): 135-142.
5. Safrin, S., and C. Grunfeld. 1999. Fat distribution and metabolic changes in patients with HIV infection. AIDS. 13: 2493-2505.
6. Behrens, G., A. Dejam, H. Schmidt, H. J. Balks, G. Brabant, T. Korner, M. Stoll, and R. E. Schmidt. 1999. Impaired glucose tolerance, beta cell function and lipid metabolism in HIV patients under treatment with protease inhibitors. AIDS. 13: F63-F70.
7. Periard, D., A. Telenti, P. Sudre, J. J. Cheseaux, P. Halfon, M. J. Reymond, S. M. Marcovina, M. P. Glauser, P. Nicod, R. Darioli, and V. Mooser. 1999. Atherogenic dyslipidemia in HIV-infected individuals treated with protease inhibitors. The Swiss HIV Cohort Study. Circulation. 100: 700-705.
8. Gallet, B., M. Pulik, P. Genet, P. Chedin, and M. Hiltgen. 1998. Vascular complications associated with use of HIV protease inhibitors. Lancet. 351: 1958-1959.
9. Vittecoq, D., L. Escaut, and J. J. Monsuez. 1998. Vascular complications associated with use of HIV protease inhibitors. Lancet. 351: 1959.
10. SoRelle, R. 1998. Vascular and lipid syndromes in selected HIV-infected patients. Circulation. 98: 829-830.
11. Krishnaswamy, G., D. S. Chi, J. L. Kelley, F. Sarubbi, J. K. Smith, and A. Peiris. 2000. The cardiovascular and metabolic complication of HIV infection. Cardiol. Rev. 8: 260-268.
12. Goldstein, J. L., and M. S. Brown. 1977. The low-density lipoprotein pathway and its relation to atherosclerosis. Annu. Rev. Biochem. 46: 897-930.
13. Liang, J. S., O. Distler, D. A. Cooper, H. Jamil, R. J. Deckelbaum, H. N. Ginsberg, and S. L. Sturley. 2001. HIV protease inhibitors protect apolipoprotein B from degradation by the proteasome: a potential mechanism for protease inhibitor-induced hyperlipidemia. Nat. Med. 7: 1327-1331.
14. Lenhard, J. M., D. K. Croom, J. E. Weiel, and D. A. Winegar. 2000. HIV protease inhibitors stimulate hepatic triglyceride synthesis. Arterioscler. Thromb. Vasc. Biol. 20: 2625-2629.
15. Riddle, T. M., D. G. Kuhel, L. A. Woollett, C. J. Fichtenbaum, and D. Y. Hui. 2001. HIV protease inhibitor induces fatty acid and sterol biosynthesis in liver and adipose tissues due to the accumulation of activated sterol regulatory element-binding proteins in the nucleus. J. Biol. Chem. 276: 37514-37519.
16. Dressman, J., J. Kincer, S. V. Matveev, L. Guo, R. N. Greenberg, T. Guerin, D. Meade, X. A. Li, W. Zhu, A. Uittenbogaard, M. E. Wilson, and E. J. Smart. 2003. HIV protease inhibitors promote atherosclerotic lesion formation independent of dyslipidemia by increasing CD36-dependent cholesteryl ester accumulation in macrophages. J. Clin. Invest. 111: 389-397.
17. Jain, R. G., and J. M. Lenhard. 2002. Select HIV protease inhibitors alter bone and fat metabolism ex vivo. J. Biol. Chem. 277: 19247-19250.
18. Dowell, P., C. Flexner, P. O. Kwiterovich, and M. D. Lane. 2000. Suppression of preadipocyte differentiation and promotion of adipocyte death by HIV protease inhibitors. J. Biol. Chem. 275: 41325-41332.
19. Wang, X., R. Sato, M. S. Brown, X. Hua, and J. L. Goldstein. 1994. SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis. Cell. 77: 53-62.
20. Brown, M. S., and J. L. Goldstein. 1997. The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell. 89: 331-340.
21. Horton, J. D., J. L. Goldstein, and M. S. Brown. 2002. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J. Clin. Invest. 109: 1125-1131.
22. Brown, M. S., and J. L. Goldstein. 1976. Receptor-mediated control of cholesterol metabolism. Science. 191: 150-154.
23. Brown, M. S., and J. L. Goldstein. 1986. A receptor-mediated pathway for cholesterol homeostasis. Science. 232: 34-47.
24. Brown, M. S., S. E. Dana, and J. L. Goldstein. 1975. Receptor-dependent hydrolysis of cholesteryl esters contained in plasma low density lipoprotein. Proc. Natl. Acad. Sci. USA. 72: 2925-2929.
25. Brown, M. S., and J. L. Goldstein. 1976. Familial hypercholesterolemia: a genetic defect in the low-density lipoprotein receptor. N. Engl. J. Med. 294: 1386-1390.
26. Beisiegel, U., W. Weber, G. Ihrke, J. Herz, and K. K. Stanley. 1989. The LDL-receptor related protein, LRP, is an apolipoprotein E binding protein. Nature. 341: 162-164.
27. Rohlmann, A., M. Gotthardt, R. E. Hammer, and J. Herz. 1998. Inducible inactivation of hepatic LRP gene by cre-mediated recombination confirms role of LRP in clearance of chylomicron remnants. J. Clin. Invest. 101: 689-695.
28. Kowal, R. C., J. Herz, J. L. Goldstein, V. Esser, and M. S. Brown. 1989. Low density lipoprotein receptor-related protein mediates uptake of cholesteryl esters derived from apoprotein E-enriched lipoproteins. Proc. Natl. Acad. Sci. USA. 86: 5810-5814.
29. Herz, J., and D. K. Strickland. 2001. LRP: a multifunctional scanvenger and signaling receptor. J. Clin. Invest. 108: 779-784.
30. Loukinova, E., S. Ranganathan, S. Kuznetsov, N. Gorlatova, M. Migliorini, D. Loukinov, P. Ulery, I. Mikhailenko, D. A. Lawrence, and D. K. Strickland. 2002. PDGF-induced tyrosine phosphorylation of the LDL receptor-related protein (LRP): evidence for integrated co-receptor function between LRP and the PDGF receptor. J. Biol. Chem. 277: 15499-15506.
31. Boucher, P., P. Liu, M. Gotthardt, T. Hiesberger, R. G. Anderson, and J. Herz. 2002. Platelet-derived growth factor mediates tyrosine phosphorylation of the cytoplasmic domain of the low density lipoprotein receptor-related protein in caveolae. J. Biol. Chem. 277: 15507-15513.
32. Boucher, P., M. Gotthardt, W. P. Li, R. G. Anderson, and J. Herz. 2003. LRP: role in vascular wall integrity and protection from atherosclerosis. Science. 300: 329-332.
33. Sato, R., J. Yang, X. Wang, M. J. Evans, Y. K. Ho, J. L. Goldstein, and M. S. Brown. 1994. Assignment of the membrane attachment, DNA binding, and transcriptional activation domains of sterol regulatory element-binding protein-1 (SREBP-1). J. Biol. Chem. 269: 17267-17273.
34. Hua, X. X., J. Sakai, Y. K. Ho, J. L. Goldstein, and M. S. Brown. 1995. Hairpin orientation of sterol regulatory element-binding protein-2 in cell membranes as determined by protease protection. J. Biol. Chem. 270: 29422-29427.
35. Mikhailenko, I., F. D. Battey, M. Migliorini, J. F. Ruiz, K. Argraves, M. Moayeri, and D. K. Strickland. 2001. Recognition of alpha 2-macroglobulin by the low density lipoprotein receptor-related protein requires the cooperation of two ligand binding cluster regions. J. Biol. Chem. 276: 39484-39491.
36. Wittmaack, F. M., M. Gåfvels, M. Bronner, H. Matsuo, K. McCrae, J. Tomaszewski, S. L. Robinson, D. K. Strickland, and J. F. Strauss III. 1995. Localization and regulation of the human VLDL/ApoE receptor: trophoblast expression predicts a role for the receptor in placental lipid transport. Endocrinology. 136: 340-348.
37. Roberts, C. J., T. M. Birkenmeier, J. J. McQuillan, S. K. Akiyama, S. S. Yamada, W. T. Chen, K. M. Yamada, and J. A. McDonald. 1988. Transforming growth factor beta stimulates the expression of fibronectin and of both subunits of the human fibronectin receptor by cultured human lung fibroblasts. J. Biol. Chem. 263: 4586-4592.
38. Ashcom, J. D., S. E. Tiller, K. Dickerson, J. L. Cravens, W. S. Argraves, and D. K. Strickland. 1990. The human A2-macroglobulin receptor: identification of a 420-kD cell surface glycoprotein specific for the activated conformation of A2-macroglobulin. J. Cell Biol. 110: 1041-1048.
39. 2-macroglobulin receptor/low density lipoprotein receptor-related protein. Multiple regulatory sites for 39-kDa receptor-associated protein. J. Biol. Chem. 267: 9035-9040.
40. Ye, J., R. B. Rawson, R. Komuro, X. Chen, U. P. Dave, R. Prywes, M. S. Brown, and J. L. Goldstein. 2000. ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs. Mol. Cell. 6: 1355-1364.
41. Heid, C. A., J. Stevens, K. J. Livak, and P. M. Williams. 1996. Real time quantitative PCR. Genome Res. 6: 986-994.
42. Goldstein, J. L., S. K. Basu, and M. S. Brown. 1983. Receptor-mediated endocytosis of low-density lipoprotein in cultured cells. Methods Enzymol. 98: 241-260.
43. DeBose-Boyd, R. A., M. S. Brown, W. P. Li, A. Nohturfft, J. L. Goldstein, and P. J. Espenshade. 1999. Transport-dependent proteolysis of SREBP: relocation of site-1 protease from Golgi to ER obviates the need for SREBP transport to Golgi. Cell. 99: 703-712.
44. Dignam, J. D., R. M. Lebovitz, and R. G. Roeder. 1983. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 11: 1475-1489.
45. Brown, M. S., J. Ye, R. B. Rawson, and J. L. Goldstein. 2000. Regulated intramembrane proteolysis: a control mechanism conserved from bacteria to humans. Cell. 100: 391-398.
46. Yokoyama, C., X. Wang, M. R. Briggs, A. Admon, J. Wu, X. Hua, J. L. Goldstein, and M. S. Brown. 1993. SREBP-1, a basic-helix-loop-helix-leucine zipper protein that controls transcription of the low density lipoprotein receptor gene. Cell. 75: 187-197.
47. Kutt, H., J. Herz, and K. K. Stanley. 1989. Structure of the low-density lipoprotein receptor-related protein (LRP) promoter. Biochim. Biophys. Acta. 1009: 229-236.
48. Kraft, H. G., S. J. Demosky, Jr., K. Schumacher, H. B. Brewer, Jr., and J. M. Hoeg. 1992. Regulation of LDL receptor, apoB, and apoE apoe protein and MRNA in Hep G2 cells. DNA Cell Biol. 11: 291-300.
49. Mazzone, T., and K. Basheeruddin. 1991. Dissociated regulation of macrophage LDL receptor and apolipoprotein E gene expression by sterol. J. Lipid Res. 32: 507-514.
50. Brown, M. S., and J. L. Goldstein. 1975. Regulation of the activity of the low density lipoprotein receptor in human fibroblasts. Cell. 6: 307-316.
51. Goldstein, J. L., M. K. Sobhani, J. R. Faust, and M. S. Brown. 1976. Heterozygous familial hypercholesterolemia: failure of normal allele to compensate for mutant allele at a regulated genetic locus. Cell. 9: 195-203.
52. Stein, J. H., M. A. Klein, J. L. Bellehumeur, P. E. McBride, D. A. Wiebe, J. D. Otvos, and J. M. Sosman. 2001. Use of human immuno-deficiency, virus-1 protease inhibitors is associated with atherogenic lipoprotein changes and endothelial dysfunction. Circulation. 104: 257-262.
53. Tsiodras, S., C. Mantzoros, S. Hammer, and M. Samore. 2000. Effects of protease inhibitors on hyperglycemia, hyerlipidemia, and lipodystrophy: a 5-year cohort study. Arch. Intern. Med. 160: 2050-2056.
54. Roth, V. R., S. Kravcik, and J. B. Angel. 1998. Development of cervical fat pads following therapy with human immunodeficiency virus type 1 protease inhibitors. Clin. Infect. Dis. 27: 65-67.
55. Hua, X., A. Nohturfft, J. L. Goldstein, and M. S. Brown. 1996. Sterol resistance in CHO cells traced to point mutation in SREBP cleavage-activating protein. Cell. 87: 415-426.
56. Nohturfft, A., M. S. Brown, and J. L. Goldstein. 1998. Topology of SREBP cleavage-activating protein, a polytopic membrane protein with a sterol-sensing domain. J. Biol. Chem. 273: 17243-17250.
57. Yang, T., P.J. Espenshade, M. E. Wright, D. Yabe, Y. Gong, R. Aebersold, J. L. Goldstein, and M. S. Brown. 2002. Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER. Cell. 110: 489-500.
58. Nohturfft, A., R. A. DeBose-Boyd, S. Scheek, J. L. Goldstein, and M. S. Brown. 1999. Sterols regulate cycling of SREBP cleavage-activating protein (SCAP) between endoplasmic reticulum and Golgi. Proc. Natl. Acad. Sci. USA. 96: 11235-11240.
59. Nohturfft, A., D. Yabe, J. L. Goldstein, M. S. Brown, and P.J. Espenshade. 2000. Regulated step in cholesterol feedback localized to budding of SCAP from ER membranes. Cell. 102: 315-323.
60. Ye, J., U. P. Dave, N. V. Grishin, J. L. Goldstein, and M. S. Brown. 2000. Asparagine-proline sequence within membrane-spanning segment of SREBP triggers intramembrane cleavage by site-2 protease. Proc. Natl. Acad. Sci. USA. 97: 5123-5128.
61. Fewell, S. W., K.J. Travers, J. S. Weissman, and J. L. Brodsky. 2001. The action of molecular chaperones in the early secretory pathway. Annu. Rev. Genet. 35: 149-191.
62. Hampton, R. Y. 2000. ER stress response: getting the UPR hand on misfolded proteins. Curr. Biol. 10: R518-R521.
63. Wang, Y., J. Shen, N. Arenzana, W. Tirasophon, R. J. Kaufman, and R. Prywes. 2000. Activation of ATF6 and an ATF6 DNA binding site by the endoplasmic reticulum stress response. J. Biol. Chem. 275: 27013-27020.
64. Werstuck, G. H., S. R. Lentz, S. Dayal, G. S. Hossain, S. K. Sood, Y. Y. Shi, J. Zhou, N. Maeda, S. K. Krisans, M. R. Malinow, and R. C. Austin. 2001. Homocysteine-induced endoplasmic reticulum stress causes dysregulation of the cholesterol and triglyceride biosynthetic pathways. J. Clin. Invest. 107: 1263-1273.
65. Xu, W., Y. Takahashi, T. Sakashita, T. Iwasaki, H. Hattori, and T. Yoshimoto. 2001. Low density lipoprotein receptor-related protein is required for macrophage-mediated oxidation of low density lipoprotein by 12/15-lipoxygenase. J. Biol. Chem. 39: 36454-36459.
66. Gaëta, B. A., I. Borthwick, and K. K. Stanley. 1994. The 5′-flanking region of the A2MR/LRP gene contains an enhancer-like cluster of Sp1 binding sites. Biochim. Biophys. Acta.. 1219: 307-313.