PCSK9 deficiency unmasks a sex- And tissue-specific subcellular distribution of the LDL and VLDL receptors in mice

Journal of Lipid Research

Volumn 56, Issue 11, 2015, Pages 2133-2142

  Roubtsova, Anna ^a   Chamberland, Ann ^a   Marcinkiewicz, Jadwiga ^a   Essalmani, Rachid ^a   Fazel, Ali ^b   Bergeron, John J ^b   Seidah, Nabil G ^a   Prat, Annik ^a  

^a CLIN RESEARCH INSTITUTE OF MONTREAL   (Canada)

^b RESEARCH INSTITUTE OF THE MCGILL UNIVERSITY HEALTH CENTRE   (Canada)

Author keywords

Cholesterol; Estrogen; LDL metabolism; Lipoproteins receptors; Liver

Indexed keywords

ADAPTOR PROTEIN; ESTRADIOL; LOW DENSITY LIPOPROTEIN RECEPTOR; LOW DENSITY LIPOPROTEIN RECEPTOR ADAPTOR PROTEIN 1; MESSENGER RNA; PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9; SERINE PROTEINASE; UNCLASSIFIED DRUG; VERY LOW DENSITY LIPOPROTEIN RECEPTOR; PCSK9 PROTEIN, MOUSE; PROPROTEIN CONVERTASE 9;

ADIPOCYTE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CELL SURFACE; CELLULAR DISTRIBUTION; CHOLESTEROL DIET; CONTROLLED STUDY; ELECTRON MICROSCOPY; ENZYME DEFICIENCY; FEMALE; GENOTYPE; IMMUNOHISTOCHEMISTRY; INTESTINE CELL; KNOCKOUT MOUSE; LIVER; LIVER CELL; MALE; MOUSE; NONHUMAN; OVARIECTOMY; PANCREAS ISLET; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; REGULATORY MECHANISM; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; ANIMAL; ANTIBODY SPECIFICITY; BLOOD; C57BL MOUSE; DEFICIENCY; ENZYMOLOGY; GENETICS; INTRAABDOMINAL FAT; METABOLISM; OBESITY; PHYSIOLOGY; PROTEIN TRANSPORT; SEXUAL DEVELOPMENT;

ADIPOSITY; ANIMALS; ESTRADIOL; FEMALE; INTRA-ABDOMINAL FAT; LIVER; MALE; MICE, INBRED C57BL; MICE, KNOCKOUT; ORGAN SPECIFICITY; PROPROTEIN CONVERTASE 9; PROPROTEIN CONVERTASES; PROTEIN TRANSPORT; RECEPTORS, LDL; RNA, MESSENGER; SERINE ENDOPEPTIDASES; SEX CHARACTERISTICS;

EID: 84948743740     PISSN: 00222275     EISSN: 15397262     Source Type: Journal    
DOI: 10.1194/jlr.M061952     Document Type: Article

References (45)

1. Seidah, N. G., and A. Prat. 2012. The biology and therapeutic targeting of the proprotein convertases. Nat. Rev. Drug Discov. 11 : 367 - 383.
2. Abifadel, M., M. Varret, J. P. Rabes, D. Allard, K. Ouguerram, M. Devillers, C. Cruaud, S. Benjannet, L. Wickham, D. Erlich, et al. 2003. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat. Genet. 34 : 154 - 156.
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. 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.
6. Denis, M., J. Marcinkiewicz, A. Zaid, D. Gauthier, S. Poirier, C. Lazure, N. G. Seidah, and A. Prat. 2012. Gene inactivation of PCSK9 reduces atherosclerosis in mice. Circulation. 125 : 894 - 901.
7. Guella, I., R. Asselta, D. Ardissino, P. A. Merlini, F. Peyvandi, S. Kathiresan, P. M. Mannucci, M. Tubaro, and S. Duga. 2010. Effects of PCSK9 genetic variants on plasma LDL cholesterol levels and risk of premature myocardial infarction in the Italian population. J. Lipid Res. 51 : 3342 - 3349.
8. Huang, Y., D. G. Ballinger, R. Stokowski, E. Beilharz, J. G. Robinson, S. Liu, R. D. Robinson, V. W. Henderson, J. E. Rossouw, and R. L. Prentice. 2012. Exploring the interaction between SNP genotype and postmenopausal hormone therapy effects on stroke risk. Genome Med. 4 : 57.
9. Zhao, Z., Y. Tuakli-Wosornu, T. A. Lagace, L. Kinch, N. V. Grishin, J. D. Horton, J. C. Cohen, and H. H. Hobbs. 2006. Molecular characterization of loss-of-function mutations in PCSK9 and identifi cation of a compound heterozygote. Am. J. Hum. Genet. 79 : 514 - 523.
10. Hooper, A. J., A. D. Marais, D. M. Tanyanyiwa, and J. R. Burnett. 2007. The C679X mutation in PCSK9 is present and lowers blood cholesterol in a Southern African population. Atherosclerosis. 193 : 445 - 448.
11. Cariou, B., K. Ouguerram, Y. Zair, R. Guerois, C. Langhi, S. Kourimate, I. Benoit, M. C. Le, C. Gayet, K. Belabbas, et al. 2009. PCSK9 dominant negative mutant results in increased LDL catabolic rate and familial hypobetalipoproteinemia. Arterioscler. Thromb. Vasc. Biol. 29 : 2191 - 2197.
12. Seidah, N. G. 2013. Proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors in the treatment of hypercholesterolemia and other pathologies. Curr. Pharm. Des. 19 : 3161 - 3172.
13. Naureckiene, S., L. Ma, K. Sreekumar, U. Purandare, C. F. Lo, Y. Huang, L. W. Chiang, J. M. Grenier, B. A. Ozenberger, J. S. Jacobsen, et al. 2003. Functional characterization of Narc 1, a novel proteinase related to proteinase K. Arch. Biochem. Biophys. 420 : 55 - 67.
14. 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.
15. 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.
16. 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.
17. Poirier, S., G. Mayer, V. Poupon, P. S. McPherson, R. Desjardins, K. Ly, M. C. Asselin, R. Day, F. J. Duclos, M. Witmer, et al. 2009. Dissection of the endogenous cellular pathways of PCSK9-induced LDLR degradation: evidence for an intracellular route. J. Biol. Chem. 284 : 28856 - 28864.
18. Timms, K. M., S. Wagner, M. E. Samuels, K. Forbey, H. Goldfi ne, S. Jammulapati, M. H. Skolnick, P. N. Hopkins, S. C. Hunt, and D. M. Shattuck. 2004. A mutation in PCSK9 causing autosomal-dominant hypercholesterolemia in a Utah pedigree. Hum. Genet. 114 : 349 - 353.
19. Zaid, A., A. Roubtsova, R. Essalmani, J. Marcinkiewicz, A. Chamberland, J. Hamelin, M. Tremblay, H. Jacques, W. Jin, J. Davignon, et al. 2008. Proprotein convertase subtilisin/kexin type 9 (PCSK9): hepatocyte-specifi c low-density lipoprotein receptor degradation and critical role in mouse liver regeneration. Hepatology. 48 : 646 - 654.
20. Mbikay, M., F. Sirois, J. Mayne, G. S. Wang, A. Chen, T. Dewpura, A. Prat, N. G. Seidah, M. Chretien, and F. W. Scott. 2010. PCSK9- defi cient mice exhibit impaired glucose tolerance and pancreatic islet abnormalities. FEBS Lett. 584 : 701 - 706.
21. Langhi, C., M. C. Le, V. Gmyr, B. Vandewalle, J. Kerr-Conte, M. Krempf, F. Pattou, P. Costet, and B. Cariou. 2009. PCSK9 is expressed in pancreatic delta-cells and does not alter insulin secretion. Biochem. Biophys. Res. Commun. 390: 1288-1293.
22. Roubtsova, A., M. N. Munkonda, Z. Awan, J. Marcinkiewicz, A. Chamberland, C. Lazure, K. Cianfl one, N. G. Seidah, and A. Prat. 2011. Circulating proprotein convertase subtilisin/kexin 9 (PCSK9) regulates VLDLR protein and triglyceride accumulation in visceral adipose tissue. Arterioscler. Thromb. Vasc. Biol. 31 : 785 - 791.
23. 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 adenovirusmediated gene delivery. J. Clin. Invest. 92 : 883 - 893.
24. Hubbard, A. L., D. A. Wall, and A. Ma. 1983. Isolation of rat hepatocyte plasma membranes. I. Presence of the three major domains. J. Cell Biol. 96 : 217 - 229.
25. Kay, D. G., W. H. Lai, M. Uchihashi, M. N. Khan, B. I. Posner, and J. J. Bergeron. 1986. Epidermal growth factor receptor kinase translocation and activation in vivo. J. Biol. Chem. 261 : 8473 - 8480.
26. Widnell, C. C., and J. C. Unkeless. 1968. Partial purifi cation of a lipoprotein with 5 ′ -nucleotidase activity from membranes of rat liver cells. Proc. Natl. Acad. Sci. USA. 61 : 1050 - 1057.
27. Ames, B. N., and D. T. Dubin. 1960. The role of polyamines in the neutralization of bacteriophage deoxyribonucleic acid. J. Biol. Chem. 235 : 769 - 775.
28. Bergeron, J. J., B. I. Posner, Z. Josefsberg, and R. Sikstrom. 1978. Intracellular polypeptide hormone receptors. The demonstration of specifi c binding sites for insulin and human growth hormone in Golgi fractions isolated from the liver of female rats. J. Biol. Chem. 253 : 4058 - 4066.
29. 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.
30. Ngo Sock, E. T., N. A. Chapados, and J. M. Lavoie. 2014. LDL receptor and Pcsk9 transcripts are decreased in liver of ovariectomized rats: effects of exercise training. Horm. Metab. Res. 46 : 550 - 555.
31. Lakoski, S. G., T. A. Lagace, J. C. Cohen, J. D. Horton, and H. H. Hobbs. 2009. Genetic and metabolic determinants of plasma PCSK9 levels. J. Clin. Endocrinol. Metab. 94 : 2537 - 2543.
32. Ghosh, M., C. Galman, M. Rudling, and B. Angelin. 2015. Influence of physiological changes in endogenous estrogen on circulating PCSK9 and LDL cholesterol. J. Lipid Res. 56 : 463 - 469.
33. Ooi, T. C., A. Raymond, M. Cousins, C. Favreau, M. Taljaard, C. Gavin, E. E. Jolly, S. Malone, L. Eapen, M. Chretien, et al. 2015. Relationship between testosterone, estradiol and circulating PCSK9: cross-sectional and interventional studies in humans. Clin. Chim. Acta. 446 : 97 - 104.
34. Li, C., M. R. Briggs, T. E. Ahlborn, F. B. Kraemer, and J. Liu. 2001. Requirement of Sp1 and estrogen receptor alpha interaction in 17beta-estradiol-mediated transcriptional activation of the low density lipoprotein receptor gene expression. Endocrinology. 142 : 1546 - 1553.
35. Bruning, J. C., P. Lingohr, J. Gillette, B. Hanstein, H. Avci, W. Krone, D. Muller-Wieland, and J. Kotzka. 2003. Estrogen receptoralpha and Sp1 interact in the induction of the low density lipoprotein- receptor. J. Steroid Biochem. Mol. Biol. 86 : 113 - 121.
36. Brown, L. M., and D. J. Clegg. 2010. Central effects of estradiol in the regulation of food intake, body weight, and adiposity. J. Steroid Biochem. Mol. Biol. 122 : 65 - 73.
37. Chen, W. J., J. L. Goldstein, and M. S. Brown. 1990. NPXY, a sequence often found in cytoplasmic tails, is required for coated pitmediated internalization of the low density lipoprotein receptor. J. Biol. Chem. 265 : 3116 - 3123.
38. Maurer, M. E., and J. A. Cooper. 2006. The adaptor protein Dab2 sorts LDL receptors into coated pits independently of AP-2 and ARH. J. Cell Sci. 119 : 4235 - 4246.
39. Hong, C., S. Duit, P. Jalonen, R. Out, L. Scheer, V. Sorrentino, R. Boyadjian, K. W. Rodenburg, E. Foley, L. Korhonen, et al. 2010. The E3 ubiquitin ligase IDOL induces the degradation of the low density lipoprotein receptor family members VLDLR and ApoER2. J. Biol. Chem. 285 : 19720 - 19726.
40. Zelcer, N., C. Hong, R. Boyadjian, and P. Tontonoz. 2009. LXR regulates cholesterol uptake through IDOL-dependent ubiquitination of the LDL receptor. Science. 325 : 100 - 104.
41. Scotti, E., M. Calamai, C. N. Goulbourne, L. Zhang, C. Hong, R. R. Lin, J. Choi, P. F. Pilch, L. G. Fong, P. Zou, et al. 2013. IDOL stimulates clathrin-independent endocytosis and multivesicular body-mediated lysosomal degradation of the low-density lipoprotein receptor. Mol. Cell. Biol. 33 : 1503 - 1514.
42. Butkinaree, C., M. Canuel, R. Essalmani, S. Poirier, S. Benjannet, M-C. Asselin, A. Roubtsova, J. Hamelin, J. Marcinkiewicz, A. Chamberland, et al. 2015. Amyloid precursor-like protein 2 and sortilin do not regulate the PCSK9-mediated low density lipoprotein receptor degradation but interact with each other. J. Biol. Chem. 290 : 18609 - 18620.
43. Frasor, J., J. M. Danes, B. Komm, K. C. Chang, C. R. Lyttle, and B. S. Katzenellenbogen. 2003. Profi ling of estrogen up- And down-regulated gene expression in human breast cancer cells: insights into gene networks and pathways underlying estrogenic control of proliferation and cell phenotype. Endocrinology. 144 : 4562 - 4574.
44. Cerillo, G., A. Rees, N. Manchanda, C. Reilly, I. Brogan, A. White, and M. Needham. 1998. The oestrogen receptor regulates NFkappaB and AP-1 activity in a cell-specifi c manner. J. Steroid Biochem. Mol. Biol. 67 : 79 - 88.
45. Parker, R. A., R. Garcia, C. S. Ryan, X. Liu, P. Shipkova, V. Livanov, P. Patel, and S. P. Ho. 2013. Bile acid and sterol metabolism with combined HMG-CoA reductase and PCSK9 suppression. J. Lipid Res. 54 : 2400 - 2409.