Induction of liver steatosis and lipid droplet formation in ATF6α-knockout mice burdened with pharmacological endoplasmic reticulum stress

Molecular Biology of the Cell

Volumn 21, Issue 17, 2010, Pages 2975-2986

  Yamamoto, Keisuke ^a   Takahara, Kazuna ^b   Oyadomari, Seiichi ^b   Okada, Tetsuya ^a,c   Sato, Takashi ^d   Harada, Akihiro ^d,e   Mori, Kazutoshi ^a,c  

^a KYOTO UNIVERSITY   (Japan)

^b UNIVERSITY OF TOKUSHIMA   (Japan)

^c JAPAN SCIENCE AND TECHNOLOGY AGENCY   (Japan)

^d GUNMA UNIVERSITY   (Japan)

^e OSAKA UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVATING TRANSCRIPTION FACTOR 6; ACTIVATING TRANSCRIPTION FACTOR 6ALPHA; ADIPOPHILIN; APOLIPOPROTEIN B100; CHOLESTEROL; FAT DROPLET; TRIACYLGLYCEROL; UNCLASSIFIED DRUG; VERY LOW DENSITY LIPOPROTEIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CELL STRAIN HEK293; CELL STRAIN HEPG2; CONTROLLED STUDY; ENDOPLASMIC RETICULUM STRESS; FATTY ACID OXIDATION; FATTY LIVER; HUMAN; HUMAN CELL; LIPID METABOLISM; LIVER CELL; MOUSE; NONHUMAN; NUCLEOTIDE SEQUENCE; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN INDUCTION;

ACTIVATING TRANSCRIPTION FACTOR 6; ANIMALS; APOLIPOPROTEIN B-100; BODY WEIGHT; ENDOPLASMIC RETICULUM; FATTY LIVER; GENE EXPRESSION REGULATION; HEK293 CELLS; HEP G2 CELLS; HUMANS; INJECTIONS, INTRAPERITONEAL; LIPID METABOLISM; LIVER; LIVER FUNCTION TESTS; MICE; MICE, KNOCKOUT; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; STRESS, PHYSIOLOGICAL; TUNICAMYCIN;

MAMMALIA; MUS;

EID: 77956232915     PISSN: 10591524     EISSN: 19394586     Source Type: Journal    
DOI: 10.1091/mbc.E09-02-0133     Document Type: Article

References (60)

1. Adachi, Y., Yamamoto, K., Okada, T., Yoshida, H., Harada, A., and Mori, K. (2008). ATF6 is a Transcription Factor Specializing in the Regulation of Quality Control Proteins in the Endoplasmic Reticulum. Cell Struct. Funct. 33, 75-89.
2. Adams, L. A., Angulo, P., and Lindor, K. D. (2005). Nonalcoholic fatty liver disease. CMAJ 172, 899-905.
3. Anstee, Q. M., and Goldin, R. D. (2006). Mouse models in non-alcoholic fatty liver disease and steatohepatitis research. Int. J. Exp. Pathol. 87, 1-16.
4. Bligh, E. G., and Dyer, W. J. (1959). A rapid method of total lipid extraction and purification. Can. J. Biochem. Physiol. 37, 911-917.
5. Borchardt, R. A., and Davis, R. A. (1987). Intrahepatic assembly of very low density lipoproteins. Rate of transport out of the endoplasmic reticulum determines rate of secretion. J. Biol. Chem. 262, 16394-16402.
6. Bradbury, M. W. (2006). Lipid metabolism and liver inflammation. I. Hepatic fatty acid uptake: possible role in steatosis. Am. J. Physiol. Gastrointest. Liver Physiol. 290, G194-G198.
7. Browning, J. D., and Horton, J. D. (2004). Molecular mediators of hepatic steatosis and liver injury. J. Clin. Invest. 114, 147-152.
8. Bukau, B., Weissman, J., and Horwich, A. (2006). Molecular chaperones and protein quality control. Cell 125, 443-451.
9. Day, C. P. (2002). Pathogenesis of steatohepatitis. Best Pract. Res. Clin. Gastroenterol. 16, 663-678.
10. Day, C. P., and James, O. F. (1998). Steatohepatitis: a tale of two "hits"? Gastroenterology 114, 842-845.
11. Duval, C., Muller, M., and Kersten, S. (2007). PPARalpha and dyslipidemia. Biochim. Biophys. Acta 1771, 961-971.
12. Fisher, E. A., and Ginsberg, H. N. (2002). Complexity in the secretory pathway: the assembly and secretion of apolipoprotein B-containing lipoproteins. J. Biol. Chem. 277, 17377-17380.
13. Harada, A., Sobue, K., and Hirokawa, N. (1990). Developmental changes of synapsin I subcellular localization in rat cerebellar neurons. Cell Struct. Funct. 15, 329-342.
14. Harrison, S. A., Kadakia, S., Lang, K. A., and Schenker, S. (2002). Nonalcoholic steatohepatitis: what we know in the new millennium. Am. J. Gastroenterol. 97, 2714-2724.
15. Haze, K., Okada, T., Yoshida, H., Yanagi, H., Yura, T., Negishi, M., and Mori, K. (2001). Identification of the G13 (cAMP-response-element-binding protein-related protein) gene product related to activating transcription factor 6 as a transcriptional activator of the mammalian unfolded protein response. Biochem. J. 355, 19-28. (Pubitemid 32304231)
16. Haze, K., Yoshida, H., Yanagi, H., Yura, T., and Mori, K. (1999). Mammalian transcription factor ATF6 is synthesized as a transmembrane protein and activated by proteolysis in response to endoplasmic reticulum stress. Mol. Biol. Cell 10, 3787-3799.
17. Hollien, J., and Weissman, J. S. (2006). Decay of endoplasmic reticulum-localized mRNAs during the unfolded protein response. Science 313, 104-107. (Pubitemid 44051264)
18. Kaufman, R. J. (1999). Stress signaling from the lumen of the endoplasmic reticulum: coordination of gene transcriptional and translational controls. Genes Dev. 13, 1211-1233.
19. Lee, A. H., Scapa, E. F., Cohen, D. E., and Glimcher, L. H. (2008). Regulation of hepatic lipogenesis by the transcription factor XBP1. Science 320, 1492-1496.
20. Martin, S., and Parton, R. G. (2006). Lipid droplets: a unified view of a dynamic organelle. Nat. Rev. Mol. Cell Biol. 7, 373-378.
21. McClain, C. J., Mokshagundam, S. P., Barve, S. S., Song, Z., Hill, D. B., Chen, T., and Deaciuc, I. (2004). Mechanisms of non-alcoholic steatohepatitis. Alcohol 34, 67-79.
22. Mori, K. (2000). Tripartite management of unfolded proteins in the endoplasmic reticulum. Cell 101, 451-454.
23. Nadanaka, S., Yoshida, H., Kano, F., Murata, M., and Mori, K. (2004). Activation of mammalian unfolded protein response is compatible with the quality control system operating in the endoplasmic reticulum. Mol. Biol. Cell 15, 2537-2548.
24. Nagata, K. (2003). HSP47 as a collagen-specific molecular chaperone: function and expression in normal mouse development. Semin. Cell. Dev. Biol. 14, 275-282.
25. Nakagawa, T., Zhu, H., Morishima, N., Li, E., Xu, J., Yankner, B. A., and Yuan, J. (2000). Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta. Nature 403, 98-103. (Pubitemid 30038529)
26. Noiva, R. (1999). Protein disulfide isomerase: the multifunctional redox chaperone of the endoplasmic reticulum. Semin. Cell. Dev. Biol. 10, 481-493.
27. Okada, T., Haze, K., Nadanaka, S., Yoshida, H., Seidah, N. G., Hirano, Y., Sato, R., Negishi, M., and Mori, K. (2003). A serine protease inhibitor prevents endoplasmic reticulum stress-induced cleavage but not transport of the membrane-bound transcription factor ATF6. J. Biol. Chem. 278, 31024-31032.
28. Okada, T., Yoshida, H., Akazawa, R., Negishi, M., and Mori, K. (2002). Distinct roles of activating transcription factor 6 (ATF6) and double-stranded RNA-activated protein kinase-like endoplasmic reticulum kinase (PERK) in transcription during the mammalian unfolded protein response. Biochem. J. 366, 585-594. (Pubitemid 35001703)
29. Oyadomari, S., Harding, H. P., Zhang, Y., Oyadomari, M., and Ron, D. (2008). Dephosphorylation of translation initiation factor 2alpha enhances glucose tolerance and attenuates hepatosteatosis in mice. Cell Metab. 7, 520-532. (Pubitemid 351729207)
30. Oyadomari, S., et al. (2006). Cotranslocational degradation protects the stressed endoplasmic reticulum from protein overload. Cell 126, 727-739. (Pubitemid 44233632)
31. Pol, A., Martin, S., Fernandez, M. A., Ferguson, C., Carozzi, A., Luetterforst, R., Enrich, C., and Parton, R. G. (2004). Dynamic and regulated association of caveolin with lipid bodies: modulation of lipid body motility and function by a dominant negative mutant. Mol. Biol. Cell 15, 99-110.
32. Pullinger, C. R., North, J. D., Teng, B. B., Rifici, V. A., Ronhild de Brito, A. E., and Scott, J. (1989). The apolipoprotein B gene is constitutively expressed in HepG2 cells: regulation of secretion by oleic acid, albumin, and insulin, and measurement of the mRNA half-life. J. Lipid Res. 30, 1065-1077.
33. Reddy, J. K., and Rao, M. S. (2006). Lipid metabolism and liver inflammation. II. Fatty liver disease and fatty acid oxidation. Am. J. Physiol. Gastrointest. Liver Physiol. 290, G852-G858.
34. Ron, D., and Habener, J. F. (1992). CHOP, a novel developmentally regulated nuclear protein that dimerizes with transcription factors C/EBP and LAP and functions as a dominant- negative inhibitor of gene transcription. Genes Dev. 6, 439-453.
35. Ron, D., and Walter, P. (2007). Signal integration in the endoplasmic reticulum unfolded protein response. Nat. Rev. Mol. Cell Biol. 8, 519-529.
36. Rutkowski, D. T., Kang, S. W., Goodman, A. G., Garrison, J. L., Taunton, J., Katze, M. G., Kaufman, R. J., and Hegde, R. S. (2007). The role of p58IPK in protecting the stressed endoplasmic reticulum. Mol. Biol. Cell 18, 3681-3691.
37. Rutkowski, D. T., et al. (2008). UPR Pathways Combine to Prevent Hepatic Steatosis Caused by ER Stress-Mediated Suppression of Transcriptional Master Regulators. Dev. Cell 15, 829-840.
38. Sambrook, J., Fritsch, E. F., and Maniatis, T. (1989). Molecular Cloning: A Laboratory Manual, Cold Spring Harbor, New York: Cold Spring Harbor Laboratory Press.
39. Sanal, M. G. (2008). The blind men 'see' the elephant-the many faces of fatty liver disease. World J. Gastroenterol. 14, 831-844.
40. Sato, R., Imanaka, T., Takatsuki, A., and Takano, T. (1990). Degradation of newly synthesized apolipoprotein B-100 in a pre-Golgi compartment. J. Biol. Chem. 265, 11880-11884.
41. Schroder, M., and Kaufman, R. J. (2005). The mammalian unfolded protein response. Annu. Rev. Biochem. 74, 739-789.
42. Shen, J., Chen, X., Hendershot, L., and Prywes, R. (2002). ER stress regulation of ATF6 localization by dissociation of BiP/GRP78 binding and unmasking of Golgi localization signals. Dev. Cell 3, 99-111. (Pubitemid 34778399)
43. Shen, X., Ellis, R. E., Sakaki, K., and Kaufman, R. J. (2005). Genetic interactions due to constitutive and inducible gene regulation mediated by the unfolded protein response in. C. elegans. PLoS Genet. 1, 355-368.
44. Tauchi-Sato, K., Ozeki, S., Houjou, T., Taguchi, R., and Fujimoto, T. (2002). The surface of lipid droplets is a phospholipid monolayer with a unique Fatty Acid composition. J. Biol. Chem. 277, 44507-44512.
45. Travers, K. J., Patil, C. K., Wodicka, L., Lockhart, D. J., Weissman, J. S., and Walter, P. (2000). Functional and genomic analyses reveal an essential coordination between the unfolded protein response and ER-associated degradation. Cell 101, 249-258.
46. Trent, M. S., Stead, C. M., Tran, A. X., and Hankins, J. V. (2006). Diversity of endotoxin and its impact on pathogenesis. J. Endotoxin Res. 12, 205-223.
47. Tsai, B., Ye, Y., and Rapoport, T. A. (2002). Retro-translocation of proteins from the endoplasmic reticulum into the cytosol. Nat. Rev. Mol. Cell Biol. 3, 246-255.
48. Uchiyama, S., Shimizu, T., and Shirasawa, T. (2006). CuZn-SOD deficiency causes ApoB degradation and induces hepatic lipid accumulation by impaired lipoprotein secretion in mice. J. Biol. Chem. 281, 31713-31719.
49. Vabulas, R. M., and Hartl, F. U. (2005). Protein synthesis upon acute nutrient restriction relies on proteasome function. Science 310, 1960-1963.
50. Villacorta, L., Garcia-Barrio, M. T., and Chen, Y. E. (2007). Transcriptional regulation of peroxisome proliferator-activated receptors and liver X receptors. Curr. Atheroscler. Rep. 9, 230-237.
51. Wei, Y., Rector, R. S., Thyfault, J. P., and Ibdah, J. A. (2008). Nonalcoholic fatty liver disease and mitochondrial dysfunction. World J. Gastroenterol. 14, 193-199.
52. Werstuck, G. H., et al. (2001). Homocysteine-induced endoplasmic reticulum stress causes dysregulation of the cholesterol and triglyceride biosynthetic pathways. J. Clin. Invest. 107, 1263-1273.
53. Wilhovsky, S., Gardner, R., and Hampton, R. (2000). HRD gene dependence of endoplasmic reticulum-associated degradation. Mol. Biol. Cell 11, 1697-1708.
54. Wu, J., Rutkowski, D. T., Dubois, M., Swathirajan, J., Saunders, T., Wang, J., Song, B., Yau, G. D., and Kaufman, R. J. (2007). ATF6alpha optimizes long-term endoplasmic reticulum function to protect cells from chronic stress. Dev. Cell 13, 351-364. (Pubitemid 47308675)
55. Yamamoto, K., Sato, T., Matsui, T., Sato, M., Okada, T., Yoshida, H., Harada, A., and Mori, K. (2007). Transcriptional induction of mammalian ER quality control proteins is mediated by single or combined action of ATF6alpha and XBP1. Dev. Cell 13, 365-376. (Pubitemid 47308680)
56. Ye, J., Rawson, R. B., Komuro, R., Chen, X., Dave, U. P., Prywes, R., Brown, M. S., and Goldstein, J. L. (2000). ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs. Mol. Cell 6, 1355-1364.
57. Yoshida, H., Okada, T., Haze, K., Yanagi, H., Yura, T., and Mori, K. (2000). ATF6 activated by proteolysis directly binds in the presence of NF-Y (CBF) to the cis-acting element responsible for the mammalian unfolded protein response. Mol. Cell. Biol. 20, 6755-6767.
58. Yoshida, H., Okada, T., Haze, K., Yanagi, H., Yura, T., Negishi, M., and Mori, K. (2001). Endoplasmic reticulum stress-induced formation of transcription factor complex ERSF including NF-Y (CBF) and activating transcription factors 6α and 6β that activates the mammalian unfolded protein response. Mol. Cell. Biol. 21, 1239-1248.
59. Zhou, M., Fisher, E. A., and Ginsberg, H. N. (1998). Regulated Co-translational ubiquitination of apolipoprotein B100. A new paradigm for proteasomal degradation of a secretory protein. J. Biol. Chem. 273, 24649-24653.
60. Zinszner, H., Kuroda, M., Wang, X., Batchvarova, N., Lightfoot, R. T., Remotti, H., Stevens, J. L., and Ron, D. (1998). CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum. Genes Dev. 12, 982-995. (Pubitemid 28204605)