FoxO3 transcription factor and Sirt6 deacetylase regulate low density lipoprotein (LDL)-cholesterol homeostasis via control of the proprotein convertase subtilisin/kexin type 9 (Pcsk9) gene expression

Journal of Biological Chemistry

Volumn 288, Issue 41, 2013, Pages 29252-29259

  Tao, Rongya ^a   Xiong, Xiwen ^a   DePinho, Ronald A ^b   Deng, Chu Xia ^c   Dong, X Charlie ^a  

^a INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^c NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BIOCHEMICAL CHARACTERISTICS; CARDIO-VASCULAR DISEASE; CHOLESTEROL HOMEOSTASIS; EPIGENETIC REGULATION; FORKHEAD TRANSCRIPTIONS; GENETIC ANALYSIS; HISTONE DEACETYLASES; LOW DENSITY LIPOPROTEINS;

AMINO ACIDS; GENES; MAMMALS; PHYSIOLOGY; TRANSCRIPTION FACTORS;

CHOLESTEROL;

HISTONE DEACETYLASE; HISTONE H3; LOW DENSITY LIPOPROTEIN CHOLESTEROL; LOW DENSITY LIPOPROTEIN RECEPTOR; LYSINE; SIRTUIN 6; TRANSCRIPTION FACTOR FKHRL1;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CHOLESTEROL METABOLISM; DEACETYLATION; ENZYME DEFICIENCY; EPIGENETICS; GENE; GENE CONTROL; GENE EXPRESSION REGULATION; LIPID DIET; LONGEVITY; LOW DENSITY LIPOPROTEIN CHOLESTEROL HOMEOSTASIS; MOUSE; NONHUMAN; PCSK9 GENE; PRIORITY JOURNAL; PROMOTER REGION; PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9 GENE; PROTEIN DEGRADATION; PROTEIN EXPRESSION;

CHOLESTEROL; EPIGENETICS; HISTONE DEACETYLASE; LIVER; SIRTUINS;

ACETYLATION; ANIMALS; BLOTTING, WESTERN; CHOLESTEROL, LDL; FORKHEAD TRANSCRIPTION FACTORS; GENE EXPRESSION REGULATION; HISTONES; HOMEOSTASIS; LIVER; LYSINE; MICE; MICE, 129 STRAIN; MICE, INBRED C57BL; MICE, KNOCKOUT; PROMOTER REGIONS, GENETIC; PROPROTEIN CONVERTASES; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RNA INTERFERENCE; SERINE ENDOPEPTIDASES; SIRTUINS;

EID: 84885637201     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M113.481473     Document Type: Article

References (59)

1. Bulbulia, R., and Armitage, J. (2012) LDL cholesterol targets. How low to go? Curr. Opin. Lipidol. 23, 265-270
2. van der Wulp, M. Y., Verkade, H. J., and Groen, A. K. (2013) Regulation of cholesterol homeostasis. Mol. Cell. Endocrinol. 368, 1-16
3. Marais, D. A., Blom, D. J., Petrides, F., Gouëffic, Y., and Lambert, G. (2012) Proprotein convertase subtilisin/kexin type 9 inhibition. Curr. Opin. Lipidol. 23, 511-517
4. Abifadel, M., Varret, M., Rabès, J. P., Allard, D., Ouguerram, K., Devillers, M., Cruaud, C., Benjannet, S., Wickham, L., Erlich, D., Derré, A., Villéger, L., Farnier, M., Beucler, I., Bruckert, E., Chambaz, J., Chanu, B., Lecerf, J. M., Luc, G., Moulin, P., Weissenbach, J., Prat, A., Krempf, M., Junien, C., Seidah, N. G., and Boileau, C. (2003) Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat. Genet. 34, 154-156
5. Lambert, G., Sjouke, B., Choque, B., Kastelein, J. J., and Hovingh, G. K. (2012) The PCSK9 decade. J. Lipid Res. 53, 2515-2524
6. Denis, M., Marcinkiewicz, J., Zaid, A., Gauthier, D., Poirier, S., Lazure, C., Seidah, N. G., and Prat, A. (2012) Gene inactivation of proprotein convertase subtilisin/kexin type 9 reduces atherosclerosis in mice. Circulation 125, 894-901
7. Maxwell, K. N., and Breslow, J. L. (2004) Adenoviral-mediated expression of Pcsk9 in mice results in a low-density lipoprotein receptor knockout phenotype. Proc. Natl. Acad. Sci. U.S.A. 101, 7100-7105
8. Rashid, S., Curtis, D. E., Garuti, R., Anderson, N. N., Bashmakov, Y., Ho, Y. K., Hammer, R. E., Moon, Y. A., and Horton, J. D. (2005) Decreased plasma cholesterol and hypersensitivity to statins in mice lacking Pcsk9. Proc. Natl. Acad. Sci. U.S.A. 102, 5374-5379
9. Lagace, T. A., Curtis, D. E., Garuti, R., McNutt, M. C., Park, S. W., Prather, H. B., Anderson, N. N., Ho, Y. K., Hammer, R. E., and Horton, J. D. (2006) Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice. J. Clin. Invest. 116, 2995-3005
10. Park, S. W., Moon, Y. A., and Horton, J. D. (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
11. Lalanne, F., Lambert, G., Amar, M. J., Chétiveaux, M., Zaïr, Y., Jarnoux, A. L., Ouguerram, K., Friburg, J., Seidah, N. G., Brewer, H. B., Jr., Krempf, M., and Costet, P. (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
12. Schmidt, R. J., Beyer, T. P., Bensch, W. R., Qian, Y. W., Lin, A., Kowala, M., Alborn, W. E., Konrad, R. J., and Cao, G. (2008) Secreted proprotein convertase subtilisin/kexin type 9 reduces both hepatic and extrahepatic lowdensity lipoprotein receptors in vivo. Biochem. Biophys. Res. Commun. 370, 634-640
13. Luo, Y., Warren, L., Xia, D., Jensen, H., Sand, T., Petras, S., Qin, W., Miller, K. S., and Hawkins, J. (2009) Function and distribution of circulating human PCSK9 expressed extrahepatically in transgenic mice. J. Lipid Res. 50, 1581-1588
14. Sullivan, D., Olsson, A. G., Scott, R., Kim, J. B., Xue, A., Gebski, V., Wasserman, S. M., and Stein, E. A. (2012) Effect of a monoclonal antibody to PCSK9 on low-density lipoprotein cholesterol levels in statin-intolerant patients. The GAUSS randomized trial. JAMA 308, 2497-2506
15. Stein, E. A., Mellis, S., Yancopoulos, G. D., Stahl, N., Logan, D., Smith, W. B., Lisbon, E., Gutierrez, M., Webb, C., Wu, R., Du, Y., Kranz, T., Gasparino, E., and Swergold, G. D. (2012) Effect of a monoclonal antibody to PCSK9 on LDL cholesterol. N. Engl. J. Med. 366, 1108-1118
16. Stein, E. A., Gipe, D., Bergeron, J., Gaudet, D., Weiss, R., Dufour, R., Wu, R., and Pordy, R. (2012) Effect of a monoclonal antibody to PCSK9, REGN727/SAR236553, to reduce low-density lipoprotein cholesterol in patients with heterozygous familial hypercholesterolaemia on stable statin dose with or without ezetimibe therapy. A phase 2 randomised controlled trial. Lancet 380, 29-36
17. Roth, E. M., McKenney, J. M., Hanotin, C., Asset, G., and Stein, E. A. (2012) Atorvastatin with or without an antibody to PCSK9 in primary hypercholesterolemia. N. Engl. J. Med. 367, 1891-1900
18. Raal, F., Scott, R., Somaratne, R., Bridges, I., Li, G., Wasserman, S. M., and Stein, E. A. (2012) Low-density lipoprotein cholesterol-lowering effects of AMG 145, a monoclonal antibody to proprotein convertase subtilisin/ kexin type 9 serine protease in patients with heterozygous familial hypercholesterolemia. The Reduction of LDL-C with PCSK9 inhibition in heterozygous familial hypercholesterolemia disorder (RUTHERFORD) randomized trial. Circulation 126, 2408-2417
19. Koren, M. J., Scott, R., Kim, J. B., Knusel, B., Liu, T., Lei, L., Bolognese, M., and Wasserman, S. M. (2012) Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 as monotherapy in patients with hypercholesterolaemia (MENDEL). A randomised, double-blind, placebo-controlled, phase 2 study. Lancet 380, 1995-2006
20. Giugliano, R. P., Desai, N. R., Kohli, P., Rogers, W. J., Somaratne, R., Huang, F., Liu, T., Mohanavelu, S., Hoffman, E. B., McDonald, S. T., Abrahamsen, T. E., Wasserman, S. M., Scott, R., Sabatine, M. S., and LAPLACE-TIMI 57 Investigators (2012) Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 in combination with a statin in patients with hypercholesterolaemia (LAPLACE-TIMI 57). A randomised, placebo-controlled, dose-ranging, phase 2 study. Lancet 380, 2007-2017
21. Dias, C. S., Shaywitz, A. J., Wasserman, S. M., Smith, B. P., Gao, B., Stolman, D. S., Crispino, C. P., Smirnakis, K. V., Emery, M. G., Colbert, A., Gibbs, J. P., Retter, M. W., Cooke, B. P., Uy, S. T., Matson, M., and Stein, E. A. (2012) Effects of AMG 145 on low-density lipoprotein cholesterol levels. Results from 2 randomized, double-blind, placebo-controlled, ascending- dose phase 1 studies in healthy volunteers and hypercholesterolemic subjects on statins. J. Am. Coll. Cardiol. 60, 1888-1898
22. Persson, L., Cao, G., Ståhle, L., Sjöberg, B. G., Troutt, J. S., Konrad, R. J., Gälman, C., Wallén, H., Eriksson, M., Hafström, I., Lind, S., Dahlin, M., Amark, P., Angelin, B., and Rudling, M. (2010) Circulating proprotein convertase subtilisin kexin type 9 has a diurnal rhythm synchronous with cholesterol synthesis and is reduced by fasting in humans. Arterioscler. Thromb. Vasc. Biol. 30, 2666-2672
23. Persson, L., Gälman, C., Angelin, B., and Rudling, M. (2009) Importance of proprotein convertase subtilisin/kexin type 9 in the hormonal and dietary regulation of rat liver low-density lipoprotein receptors. Endocrinology 150, 1140-1146
24. Langhi, C., Le May, C., Kourimate, S., Caron, S., Staels, B., Krempf, M., Costet, P., and Cariou, B. (2008) Activation of the farnesoid X receptor represses PCSK9 expression in human hepatocytes. FEBS Lett. 582, 949-955
25. Cameron, J., Ranheim, T., Kulseth, M. A., Leren, T. P., and Berge, K. E. (2008) Berberine decreases PCSK9 expression in HepG2 cells. Atherosclerosis 201, 266-273
26. Cao, A., Wu, M., Li, H., and Liu, J. (2011) Janus kinase activation by cytokine oncostatin M decreases PCSK9 expression in liver cells. J. Lipid Res. 52, 518-530
27. Wu, M., Dong, B., Cao, A., Li, H., and Liu, J. (2012) Delineation of molecular pathways that regulate hepatic PCSK9 and LDL receptor expression during fasting in normolipidemic hamsters. Atherosclerosis 224, 401-410
28. Duan, Y., Chen, Y., Hu, W., Li, X., Yang, X., Zhou, X., Yin, Z., Kong, D., Yao, Z., Hajjar, D. P., Liu, L., Liu, Q., and Han, J. (2012) Peroxisome proliferator- activated receptor γ activation by ligands and dephosphorylation induces proprotein convertase subtilisin kexin type 9 and low density lipoprotein receptor expression. J. Biol. Chem. 287, 23667-23677
29. Costet, P., Cariou, B., Lambert, G., Lalanne, F., Lardeux, B., Jarnoux, A. L., Grefhorst, A., Staels, B., and Krempf, M. (2006) Hepatic PCSK9 expression is regulated by nutritional status via insulin and sterol regulatory elementbinding protein 1c. J. Biol. Chem. 281, 6211-6218
30. Kourimate, S., Le May, C., Langhi, C., Jarnoux, A. L., Ouguerram, K., Zaïr, Y., Nguyen, P., Krempf, M., Cariou, B., and Costet, P. (2008) Dual mechanisms for the fibrate-mediated repression of proprotein convertase subtilisin/ kexin type 9. J. Biol. Chem. 283, 9666-9673
31. Li, H., Dong, B., Park, S. W., Lee, H. S., Chen, W., and Liu, J. (2009) Hepatocyte nuclear factor 1α plays a critical role in PCSK9 gene transcription and regulation by the natural hypocholesterolemic compound berberine. J. Biol. Chem. 284, 28885-28895
32. Browning, J. D., and Horton, J. D. (2010) Fasting reduces plasma proprotein convertase, subtilisin/kexin type 9, and cholesterol biosynthesis in humans. J. Lipid Res. 51, 3359-3363
33. Jeong, H. J., Lee, H. S., Kim, K. S., Kim, Y. K., Yoon, D., and Park, S. W. (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
34. Dong, B.,Wu,M., Li, H., Kraemer, F. B., Adeli, K., Seidah, N. G., Park, S. W., and Liu, J. (2010) Strong induction of PCSK9 gene expression through HNF1α and SREBP2. Mechanism for the resistance to LDL-cholesterol lowering effect of statins in dyslipidemic hamsters. J. Lipid Res. 51, 1486-1495
35. Li, H., and Liu, J. (2012) The novel function of HINFP as a co-activator in sterol-regulated transcription of PCSK9 in HepG2 cells. Biochem. J. 443, 757-768
36. Ai, D., Chen, C., Han, S., Ganda, A., Murphy, A. J., Haeusler, R., Thorp, E., Accili, D., Horton, J. D., and Tall, A. R. (2012) Regulation of hepatic LDL receptors by mTORC1 and PCSK9 in mice. J. Clin. Invest. 122, 1262-1270
37. Maxwell, K. N., Soccio, R. E., Duncan, E. M., Sehayek, E., and Breslow, J. L. (2003) Novel putative SREBP and LXR target genes identified by microarray analysis in liver of cholesterol-fed mice. J. Lipid Res. 44, 2109-2119
38. Kim, H. S., Xiao, C., Wang, R. H., Lahusen, T., Xu, X., Vassilopoulos, A., Vazquez-Ortiz, G., Jeong, W. I., Park, O., Ki, S. H., Gao, B., and Deng, C. X. (2010) Hepatic-specific disruption of SIRT6 in mice results in fatty liver formation due to enhanced glycolysis and triglyceride synthesis. Cell Metab. 12, 224-236
39. Tao, R., Wei, D., Gao, H., Liu, Y., DePinho, R. A., and Dong, X. C. (2011) Hepatic FoxOs regulate lipid metabolism via modulation of expression of the nicotinamide phosphoribosyltransferase gene. J. Biol. Chem. 286, 14681-14690
40. Paik, J. H., Kollipara, R., Chu, G., Ji, H., Xiao, Y., Ding, Z., Miao, L., Tothova, Z., Horner, J. W., Carrasco, D. R., Jiang, S., Gilliland, D. G., Chin, L., Wong, W. H., Castrillon, D. H., and DePinho, R. A. (2007) FoxOs are lineage-restricted redundant tumor suppressors and regulate endothelial cell homeostasis. Cell 128, 309-323
41. Dong, X. C., Copps, K. D., Guo, S., Li, Y., Kollipara, R., DePinho, R. A., and White, M. F. (2008) Inactivation of hepatic Foxo1 by insulin signaling is required for adaptive nutrient homeostasis and endocrine growth regulation. Cell Metab. 8, 65-76
42. Zhao, J., Brault, J. J., Schild, A., Cao, P., Sandri, M., Schiaffino, S., Lecker, S. H., and Goldberg, A. L. (2007) FoxO3 coordinately activates protein degradation by the autophagic/lysosomal and proteasomal pathways in atrophying muscle cells. Cell Metab. 6, 472-483
43. Tao, R., Xiong, X., Depinho, R. A., Deng, C. X., and Dong, X. C. (2013) Hepatic SREBP-2 and cholesterol biosynthesis are regulated by FoxO3 and Sirt6. J. Lipid Res. 54, 2745-2753
44. Yang, B., Zwaans, B. M., Eckersdorff, M., and Lombard, D. B. (2009) The sirtuin SIRT6 deacetylates H3 K56Ac in vivo to promote genomic stability. Cell Cycle 8, 2662-2663
45. Michishita, E., McCord, R. A., Boxer, L. D., Barber, M. F., Hong, T., Gozani, O., and Chua, K. F. (2009) Cell cycle-dependent deacetylation of telomeric histone H3 lysine K56 by human SIRT6. Cell Cycle 8, 2664-2666
46. Michishita, E., McCord, R. A., Berber, E., Kioi, M., Padilla-Nash, H., Damian, M., Cheung, P., Kusumoto, R., Kawahara, T. L., Barrett, J. C., Chang, H. Y., Bohr, V. A., Ried, T., Gozani, O., and Chua, K. F. (2008) SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin. Nature 452, 492-496
47. Kawahara, T. L., Michishita, E., Adler, A. S., Damian, M., Berber, E., Lin, M., McCord, R. A., Ongaigui, K. C., Boxer, L. D., Chang, H. Y., and Chua, K. F. (2009) SIRT6 links histone H3 lysine 9 deacetylation to NF-κB-dependent gene expression and organismal life span. Cell 136, 62-74
48. Dominy, J. E., Jr., Lee, Y., Jedrychowski, M. P., Chim, H., Jurczak, M. J., Camporez, J. P., Ruan, H. B., Feldman, J., Pierce, K., Mostoslavsky, R., Denu, J. M., Clish, C. B., Yang, X., Shulman, G. I., Gygi, S. P., and Puigserver, P. (2012) The deacetylase Sirt6 activates the acetyltransferase GCN5 and suppresses hepatic gluconeogenesis. Mol. Cell 48, 900-913
49. Kanfi, Y., Peshti, V., Gil, R., Naiman, S., Nahum, L., Levin, E., Kronfeld-Schor, N., and Cohen, H. Y. (2010) SIRT6 protects against pathological damage caused by diet-induced obesity. Aging Cell 9, 162-173
50. van der Vos, K. E., and Coffer, P. J. (2008) FOXO-binding partners. It takes two to tango. Oncogene 27, 2289-2299
51. Zhang, W., Patil, S., Chauhan, B., Guo, S., Powell, D. R., Le, J., Klotsas, A., Matika, R., Xiao, X., Franks, R., Heidenreich, K. A., Sajan, M. P., Farese, R. V., Stolz, D. B., Tso, P., Koo, S. H., Montminy, M., and Unterman, T. G. (2006) FoxO1 regulates multiple metabolic pathways in the liver. Effects on gluconeogenic, glycolytic, and lipogenic gene expression. J. Biol. Chem. 281, 10105-10117
52. Zhang, K., Li, L., Qi, Y., Zhu, X., Gan, B., DePinho, R. A., Averitt, T., and Guo, S. (2012) Hepatic suppression of Foxo1 and Foxo3 causes hypoglycemia and hyperlipidemia in mice. Endocrinology 153, 631-646
53. Niesen, M., Bedi, M., and Lopez, D. (2008) Diabetes alters LDL receptor and PCSK9 expression in rat liver. Arch Biochem. Biophys. 470, 111-115
54. Kanfi, Y., Naiman, S., Amir, G., Peshti, V., Zinman, G., Nahum, L., BarJoseph, Z., and Cohen, H. Y. (2012) The sirtuin SIRT6 regulates lifespan in male mice. Nature 483, 218-221
55. Mostoslavsky, R., Chua, K. F., Lombard, D. B., Pang, W. W., Fischer, M. R., Gellon, L., Liu, P., Mostoslavsky, G., Franco, S., Murphy, M. M., Mills, K. D., Patel, P., Hsu, J. T., Hong, A. L., Ford, E., Cheng, H. L., Kennedy, C., Nunez, N., Bronson, R., Frendewey, D., Auerbach, W., Valenzuela, D., Karow, M., Hottiger, M. O., Hursting, S., Barrett, J. C., Guarente, L., Mulligan, R., Demple, B., Yancopoulos, G. D., and Alt, F. W. (2006) Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Cell 124, 315-329
56. Anselmi, C. V., Malovini, A., Roncarati, R., Novelli, V., Villa, F., Condorelli, G., Bellazzi, R., and Puca, A. A. (2009) Association of the FOXO3A locus with extreme longevity in a southern Italian centenarian study. Rejuvenation Res. 12, 95-104
57. Flachsbart, F., Caliebe, A., Kleindorp, R., Blanché, H., von Eller-Eberstein, H., Nikolaus, S., Schreiber, S., and Nebel, A. (2009) Association of FOXO3A variation with human longevity confirmed in German centenarians. Proc. Natl. Acad. Sci. U.S.A. 106, 2700-2705
58. Soerensen, M., Dato, S., Christensen, K., McGue, M., Stevnsner, T., Bohr, V. A., and Christiansen, L. (2010) Replication of an association of variation in the FOXO3A gene with human longevity using both case-control and longitudinal data. Aging Cell 9, 1010-1017
59. Willcox, B. J., Donlon, T. A., He, Q., Chen, R., Grove, J. S., Yano, K., Masaki, K. H., Willcox, D. C., Rodriguez, B., and Curb, J. D. (2008) FOXO3A genotype is strongly associated with human longevity. Proc. Natl. Acad. Sci. U.S.A. 105, 13987-13992