Plasma PCSK9 preferentially reduces liver LDL receptors in mice

Journal of Lipid Research

Volumn 49, Issue 6, 2008, Pages 1303-1311

  Grefhorst, Aldo ^a   McNutt, Markey C ^a   Lagace, Thomas A ^a   Horton, Jay D ^a  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

Author keywords

LDL cholesterol; Proprotein convertase subtilisin kexin type 9; Sterol regulatory element binding protein

Indexed keywords

LOW DENSITY LIPOPROTEIN RECEPTOR; PROPROTEIN CONVERTASE SUBTILISIN KEXIN 9; SERINE PROTEINASE; UNCLASSIFIED DRUG; PCSK9 PROTEIN, MOUSE; PRIMER DNA; RECOMBINANT PROTEIN;

ANIMAL EXPERIMENT; ARTICLE; CATALYSIS; CONTROLLED STUDY; HALF LIFE TIME; HUMAN; KINETICS; LIPOPROTEIN BLOOD LEVEL; LIVER; MALE; MOUSE; MUTATION; NONHUMAN; PLASMA; PRIORITY JOURNAL; PROTEIN METABOLISM; ANIMAL; BLOOD; METABOLISM; NUCLEOTIDE SEQUENCE; WESTERN BLOTTING;

ANIMALS; BASE SEQUENCE; BLOTTING, WESTERN; DNA PRIMERS; LIVER; MALE; MICE; RECEPTORS, LDL; RECOMBINANT PROTEINS; SERINE ENDOPEPTIDASES;

EID: 48349092091     PISSN: 00222275     EISSN: 15397262     Source Type: Journal    
DOI: 10.1194/jlr.M800027-JLR200     Document Type: Article

References (30)

1. Rashid, S., D. E. Curtis, R. Garuti, N. N. Anderson, Y. Bashmakov, Y. K. Ho, R. E. Hammer, Y-A. Moon, and J. D. Horton. 2005. Decreased plasma cholesterol and hypersensitivity to statins in mice lacking Pcsk9. Proc. Natl. Acad. Sci. USA. 102: 5374-5379.
2. Park, S. W., Y-A. Moon, and J. D. Horton. 2004. Post-transcriptional regulation of low density lipoprotein receptor protein by proprotein convertase subtilisin/kexin type 9a in mouse liver. J. Biol. Chem. 279: 50630-50638.
3. Maxwell, K. N., and J. L. Breslow. 2004. Adenoviral-mediated expression of Pcsk9 in mice results in a low-density lipoprotein receptor knockout phenotype. Proc. Natl. Acad. Sci. USA. 101: 7100-7105.
4. Benjannet, S., D. Rhainds, R. Essalmani, J. Mayne, L. Wickham, W. Jin, M. C. Asselin, J. Hamelin, M. Varret, D. Allard, et al. 2004. NARC-1/PCSK9 and its natural mutants: zymogen cleavage and effects on the low density lipoprotein (LDL) receptor and LDL cholesterol. J. Biol. Chem. 279: 48865-48875.
5. Lalanne, F., G. Lambert, M. J. A. Amar, M. Chetiveaux, Y. Zair, A-L. Jarnoux, K. Ouguerram, J. Friburg, N. G. Seidah, H. B. Brewer, Jr., et al. 2005. Wild-type PCSK9 inhibits LDL clearance but does not affect apoB-containing lipoprotein production in mouse and cultured cells. J. Lipid Res. 46: 1312-1319. (Pubitemid 43109846)
6. Abifadel, M., M. Varret, J-P. Rabès, K. Ouguerram, M. Devillers, C. Cruaud, S. Benjannet, L. Wickham, D. Erlich, L. Villéger, et al. 2003. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat. Genet. 34: 154-156.
7. Cohen, J., A. Pertsemlidis, I. K. Kotowski, R. Graham, C. K. Garcia, and H. H. Hobbs. 2005. Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9. Nat. Genet. 37: 161-165.
8. Cohen, J. C., E. Boerwinkle, T. H. Moseley, and H. H. Hobbs. 2006. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N. Engl. J. Med. 354: 1264-1272.
9. Scartezini, M., C. Hubbart, R. A. Whittall, J. A. Cooper, A. H. Neil, and S. E. Humphries. 2007. The PCSK9 gene R46L variant is associated with lower plasma lipid levels and cardiovascular risk in healthy UK men. Clin. Sci. 113: 435-441.
10. Lagace, T. A., D. E. Curtis, R. Garuti, M. C. McNutt, S. W. Park, H. B. Prather, N. N. Anderson, Y. K. Ho, R. E. Hammer, and J. D. Horton. 2006. Secreted PCSK9 decreases LDL receptors in hepatocytes and in livers of parabiotic mice. J. Clin. Invest. 116: 2995-3005.
11. Mayne, J., A. Raymond, A. Chaplin, M. Cousins, N. Kaefer, C. Gyamera-Acheampong, N. G. Seidah, M. Mbikay, M. Chretien, and T. C. Ooi. 2007. Plasma PCSK9 levels correlate with cholesterol in men but not in women. Biochem. Biophys. Res. Commun. 361: 451-456.
12. Alborn, W. E., G. Cao, H. E. Careskey, Y-W. Qian, D. R. Subramaniam, J. Davies, E. M. Conner, and R. J. Konrad. 2007. Serum proprotein convertase subtilisin kexin type 9 is correlated directly with serum LDL cholesterol. Clin. Chem. 53: 1814-1819.
13. Zhang, D-W., T. A. Lagace, R. Garuti, Z. Zhao, M. McDonald, J. D. Horton, J. C. Cohen, and H. H. Hobbs. 2007. Binding of proprotein convertase subtilisin/kexin type 9 to epidermal growth factor-like repeat A of low density lipoprotein receptor decreases receptor recycling and increases degradation. J. Biol. Chem. 282: 18602-18612.
14. Kwon, H. J., T. A. Lagace, M. C. McNutt, J. D. Horton, and J. Deisenhofer. 2008. Molecular basis for LDL receptor recognition by PCSK9. Proc. Natl. Acad. Sci. USA. 105: 1820-1825.
15. Maxwell, K. N., E. A. Fisher, and J. L. Breslow. 2005. Overexpression of PCSK9 accelerates the degradation of the LDLR in a post-endoplasmic reticulum compartment. Proc. Natl. Acad. Sci. USA. 102: 2069-2074.
16. Nassoury, N., D. A. Blasiole, A. Tebon Oler, S. Benjannet, J. Hamelin, V. Poupon, P. S. McPherson, A. D. Attie, A. Prat, and N. G. Seidah. 2007. The cellular trafficking of the secretory proprotein convertase PCSK9 and its dependence on the LDLR. Traffic. 8: 718-732. (Pubitemid 46785153)
17. Reeves, P. J., R. L. Thurmond, and H. G. Khorana. 1996. Structure and function in rhodopsin: high level expression of a synthetic bovine opsin gene and its mutants in stable mammalian cell lines. Proc. Natl. Acad. Sci. USA. 93: 11487-11492.
18. McNutt, M. C., T. A. Lagace, and J. D. Horton. 2007. Catalytic activity is not required for secreted PCSK9 to reduce low density lipoprotein receptors in HepG2 cells. J. Biol. Chem. 282: 20799-20803.
19. Ishibashi, S., M. S. Brown, J. L. Goldstein, R. D. Gerard, R. E. Hammer, and J. Herz. 1993. Hypercholesterolemia in low density lipoprotein receptor knockout mice and its reversal by adenovirus-mediated gene delivery. J. Clin. Invest. 92: 883-893.
20. Shimano, H., J. D. Horton, R. E. Hammer, I. Shimomura, M. S. Brown, and J. L. Goldstein. 1996. Overproduction of cholesterol and fatty acids causes massive liver enlargement in transgenic mice expressing truncated SREBP-1a. J. Clin. Invest. 98: 1575-1584.
21. Horton, J. D., H. Shimano, R. L. Hamilton, M. S. Brown, and J. L. Goldstein. 1999. Disruption of LDL receptor gene in transgenic SREBP-1a mice unmasks hyperlipidemia resulting from production of lipid-rich VLDL. J. Clin. Invest. 103: 1067-1076.
22. Engelking, L. J., H. Kuriyama, R. E. Hammer, J. D. Horton, M. S. Brown, J. L. Goldstein, and G. Liang. 2004. Overexpression of Insig-1 in the livers of transgenic mice inhibits SREBP processing and reduces insulin-stimulated lipogenesis. J. Clin. Invest. 113: 1168-1175.
23. Kovanen, P. T., J. L. Goldstein, D. A. Chappell, and M. S. Brown. 1980. Regulation of low density lipoprotein receptors by adrenocorticotropin in the adrenal gland of mice and rats in vivo. J. Biol. Chem. 255: 5591-5598.
24. Fisher, T. S., P. L. Surdo, S. Pandit, M. Mattu, J. C. Santoro, D. Wisniewski, R. T. Cummings, A. Calzetta, R. M. Cubbon, P. A. Fischer, et al. 2007. Effects of pH and low density lipoprotein (LDL) on PCSK9-dependent LDL receptor regulation. J. Biol. Chem. 282: 20502-20512.
25. Cunningham, D., D. E. Danley, K. F. Geoghegan, M. C. Griffor, J. L. Hawkins, T. A. Subashi, A. H. Varghese, M. J. Ammirati, J. S. Culp, L. R. Hoth, et al. 2007. Structural and biophysical studies of PCSK9 and its mutants linked to familial hypercholesterolemia. Nat. Struct. Mol. Biol. 14: 413-419.
26. Seidah, N. G., S. Benjannet, L. Wickham, J. Marcinkiewicz, S. B. Jasmin, S. Stifani, A. Basak, A. Prat, and M. Chretien. 2003. The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation. Proc. Natl. Acad. Sci. USA. 100: 928-933.
27. Li, J., C. Tumanut, J-A. Gavigan, W-J. Huang, E. N. Hampton, R. Tumanut, K. F. Suen, J. W. Trauger, G. Spraggon, S. A. Lesley, et al. 2007. Secreted PCSK9 promotes LDL receptor degradation independently of proteolytic activity. Biochem. J. 406: 203-207. (Pubitemid 47310950)
28. 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.
29. Horton, J. D., N. A. Shah, J. A. Warrington, N. N. Anderson, S. W. Park, M. S. Brown, and J. L. Goldstein. 2003. Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes. Proc. Natl. Acad. Sci. USA. 100: 12027-12032.
30. Jeong, H. J., H-S. Lee, K-S. Kim, Y-K. Kim, D. Yoon, and S. W. Park. 2008. Sterol-dependent regulation of proprotein convertase subtilisin/kexin type 9 expression by sterol-regulatory element binding protein-2. J. Lipid Res. 49: 399-409.