Phenformin activates the unfolded protein response in an AMP-activated protein kinase (AMPK)-dependent manner

Journal of Biological Chemistry

Volumn 288, Issue 19, 2013, Pages 13631-13638

  Yang, Liu ^a   Sha, Haibo ^b   Davisson, Robin L ^c   Qi, Ling ^a,b  

^a Molecular and Cell Biology   (United States)

^b Division of Nutritional Sciences   (United States)

^c Department of Molecular Biology and Genetics   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMP-ACTIVATED PROTEIN KINASE; METABOLIC SIGNALS; METABOLIC STRESS; PHENFORMIN; UNFOLDED PROTEIN RESPONSE;

BIOELECTRIC POTENTIALS;

CROSSTALK;

HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; PANCREATIC ENDOPLASMIC RETICULUM KINASE; PHENFORMIN; PROTEIN IRE1; PROTEIN IRE1ALPHA; PROTEIN KINASE; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CELL STRAIN 3T3; CELL STRAIN HEPG2; CONTROLLED STUDY; DRUG EFFECT; ENZYME ACTIVATION; ENZYME PHOSPHORYLATION; FIBROBLAST; MOUSE; NONHUMAN; PLASMID; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; UNFOLDED PROTEIN RESPONSE;

AMP-ACTIVATED PROTEIN KINASE (AMPK); ANTI-DIABETIC DRUG; BIGUANIDE; ENDOPLASMIC RETICULUM STRESS; ENERGY METABOLISM; IRE1Α; PERK; SIGNALING; UNFOLDED PROTEIN RESPONSE;

3T3-L1 CELLS; ADENYLATE KINASE; AMINOIMIDAZOLE CARBOXAMIDE; ANIMALS; DNA-BINDING PROTEINS; EIF-2 KINASE; ENDORIBONUCLEASES; ENZYME ACTIVATORS; GENE KNOCKOUT TECHNIQUES; HEP G2 CELLS; HUMANS; HYPOGLYCEMIC AGENTS; MICE; PHENFORMIN; PHOSPHORYLATION; PROTEIN PROCESSING, POST-TRANSLATIONAL; PROTEIN-SERINE-THREONINE KINASES; RIBONUCLEOTIDES; SIGNAL TRANSDUCTION; TRANSCRIPTION FACTORS; UNFOLDED PROTEIN RESPONSE;

EID: 84877689761     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M113.462762     Document Type: Article

References (54)

1. Sha, H., He, Y., Yang, L., and Qi, L. (2011) Stressed out about obesity: IRE1α-XBP1 in metabolic disorders. Trends Endocrinol. Metab. 22, 374-381
2. Wang, S., and Kaufman, R. J. (2012) The impact of the unfolded protein response on human disease. J. Cell Biol. 197, 857-867
3. Walter, P., and Ron, D. (2011) The unfolded protein response: from stress pathway to homeostatic regulation. Science 334, 1081-1086
4. He, Y., Beatty, A., Han, X., Ji, Y., Ma, X., Adelstein, R. S., Yates, J. R., 3rd, Kemphues, K., and Qi, L. (2012) Nonmuscle myosin IIB links cytoskeleton to IRE1α signaling during ER stress. Dev. Cell 23, 1141-1152
5. Shamu, C. E., and Walter, P. (1996) Oligomerization and phosphorylation of the Ire1p kinase during intracellular signaling from the endoplasmic reticulum to the nucleus. EMBO J. 15, 3028-3039
6. Korennykh, A. V., Egea, P. F., Korostelev, A. A., Finer-Moore, J., Zhang, C., Shokat, K. M., Stroud, R. M., and Walter, P. (2009) The unfolded protein response signals through high-order assembly of Ire1. Nature 457, 687-693
7. Liou, H. C., Boothby, M. R., Finn, P. W., Davidon, R., Nabavi, N., Zeleznik-Le, N. J., Ting, J. P., and Glimcher, L. H. (1990) A new member of the leucine zipper class of proteins that binds to the HLA DRα promoter. Science 247, 1581-1584
8. He, Y., Sun, S., Sha, H., Liu, Z., Yang, L., Xue, Z., Chen, H., and Qi, L. (2010) Emerging roles for XBP1, a sUPeR transcription factor. Gene Expr. 15, 13-25
9. Liu, C. Y., Schröder, M., and Kaufman, R. J. (2000) Ligand-independent dimerization activates the stress response kinases IRE1 and PERK in the lumen of the endoplasmic reticulum. J. Biol. Chem. 275, 24881-24885
10. Harding, H. P., Zhang, Y., and Ron, D. (1999) Protein translation and folding are coupled by an endoplasmic reticulum-resident kinase. Nature 397, 271-274
11. Lu, P. D., Harding, H. P., and Ron, D. (2004) Translation reinitiation at alternative open reading frames regulates gene expression in an integrated stress response. J. Cell Biol. 167, 27-33
12. Chen, X., Shen, J., and Prywes, R. (2002) The luminal domain of ATF6 senses endoplasmic reticulum (ER) stress and causes translocation of ATF6 from the ER to the Golgi. J. Biol. Chem. 277, 13045-13052
13. Tatu, U., Braakman, I., and Helenius, A. (1993) Membrane glycoprotein folding, oligomerization and intracellular transport: effects of dithiothreitol in living cells. EMBO J. 12, 2151-2157
14. 2+-ATPase. Proc. Natl. Acad. Sci. U.S.A. 87, 2466-2470
15. Dennis, J. W., Granovsky, M., and Warren, C. E. (1999) Protein glycosylation in development and disease. Bio Essays 21, 412-421
16. Ozcan, U., Cao, Q., Yilmaz, E., Lee, A.-H., Iwakoshi, N. N., Ozdelen, E., Tuncman, G., Görgün, C., Glimcher, L. H., and Hotamisligil, G. S. (2004) Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science 306, 457-461
17. Yang, L., Xue, Z., He, Y., Sun, S., Chen, H., and Qi, L. (2010) A Phos-tagbased method reveals the extent of physiological endoplasmic reticulum stress. PLoS ONE 5, e11621
18. Mao, T., Shao, M., Qiu, Y., Huang, J., Zhang, Y., Song, B., Wang, Q., Jiang, L., Liu, Y., Han, J. D., Cao, P., Li, J., Gao, X., Rui, L., Qi, L., Li, W., and Liu, Y. (2011) PKA phosphorylation couples hepatic inositol-requiring enzyme 1α to glucagon signaling in glucose metabolism. Proc. Natl. Acad. Sci. U.S.A. 108, 15852-15857
19. Qi, L., Yang, L., and Chen, H. (2011) Detecting and quantitating physiological endoplasmic reticulum stress. Methods Enzymol. 490, 137-146
20. Sha, H., He, Y., Chen, H., Wang, C., Zenno, A., Shi, H., Yang, X., Zhang, X., and Qi, L. (2009) The IRE1α-XBP1 pathway of the unfolded protein response is required for adipogenesis. Cell Metab. 9, 556-564
21. Gwinn, D. M., Shackelford, D. B., Egan, D. F., Mihaylova, M. M., Mery, A., Vasquez, D. S., Turk, B. E., and Shaw, R. J. (2008) AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol. Cell 30, 214-226
22. Xue, Z., He, Y., Ye, K., Gu, Z., Mao, Y., and Qi, L. (2011) A conserved structural determinant located at the interdomain region of mammalian inositol-requiring enzyme 1α. J. Biol. Chem. 286, 30859-30866
23. Hetz, C., Bernasconi, P., Fisher, J., Lee, A. H., Bassik, M. C., Antonsson, B., Brandt, G. S., Iwakoshi, N. N., Schinzel, A., Glimcher, L. H., and Korsmeyer, S. J. (2006) Proapoptotic BAX and BAK modulate the unfolded protein response by a direct interaction with IRE1α. Science 312, 572-576
24. Young, C. N., Cao, X., Guruju, M. R., Pierce, J. P., Morgan, D. A., Wang, G., Iadecola, C., Mark, A. L., and Davisson, R. L. (2012) ER stress in the brain subfornical organ mediates angiotensin-dependent hypertension. J. Clin. Invest. 122, 3960-3964
25. Davidoff, F. (1968) Effects of guanidine derivatives on mitochondrial function. I. Phenethylbiguanide inhibition of respiration in mitochondria from guinea pig and rat tissues. J. Clin. Invest. 47, 2331-2343
26. Chance, B., Williams, G. R., and Hollunger, G. (1963) Inhibition of electron and energy transfer in mitochondria. I. Effects of Amytal, thiopental, rotenone, progesterone, and methylene glycol. J. Biol. Chem. 238, 418-431
27. Sols, A., and Crane, R. K. (1954) Substrate specificity of brain hexokinase. J. Biol. Chem. 210, 581-595
28. Brown, E. J., Albers, M. W., Shin, T. B., Ichikawa, K., Keith, C. T., Lane, W. S., and Schreiber, S. L. (1994) A mammalian protein targeted by G1-arresting rapamycin-receptor complex. Nature 369, 756-758
29. Wang, X. Z., Lawson, B., Brewer, J. W., Zinszner, H., Sanjay, A., Mi, L. J., Boorstein, R., Kreibich, G., Hendershot, L. M., and Ron, D. (1996) Signals from the stressed endoplasmic reticulum induce C/EBP-homologous protein (CHOP/GADD153). Mol. Cell. Biol. 16, 4273-4280
30. Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., Wu, M., Ventre, J., Doebber, T., Fujii, N., Musi, N., Hirshman, M. F., Goodyear, L. J., and Moller, D. E. (2001) Role of AMP-activated protein kinase in mechanism of metformin action. J. Clin. Invest. 108, 1167-1174
31. Hawley, S. A., Boudeau, J., Reid, J. L., Mustard, K. J., Udd, L., Mäkelä, T. P., Alessi, D. R., and Hardie, D. G. (2003) Complexes between the LKB1 tumor suppressor, STRADα/β and MO25α/β are upstream kinases in the AMP-activated protein kinase cascade. J. Biol. 2, 28
32. Lizcano, J. M., Göransson, O., Toth, R., Deak, M., Morrice, N. A., Boudeau, J., Hawley, S. A., Udd, L., Mäkelä, T. P., Hardie, D. G., and Alessi, D. R. (2004) LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1. EMBO J. 23, 833-843
33. Sullivan, J. E., Brocklehurst, K. J., Marley, A. E., Carey, F., Carling, D., and Beri, R. K. (1994) Inhibition of lipolysis and lipogenesis in isolated rat adipocytes with AICAR, a cell-permeable activator of AMP-activated protein kinase. FEBS Lett. 353, 33-36
34. Dong, Y., Zhang, M., Wang, S., Liang, B., Zhao, Z., Liu, C., Wu, M., Choi, H. C., Lyons, T. J., and Zou, M. H. (2010) Activation of AMP-activated protein kinase inhibits oxidized LDL-triggered endoplasmic reticulum stress in vivo. Diabetes 59, 1386-1396
35. Lu, J., Wang, Q., Huang, L., Dong, H., Lin, L., Lin, N., Zheng, F., and Tan, J. (2012) Palmitate causes endoplasmic reticulum stress and apoptosis in human mesenchymal stem cells: prevention by AMPK activator. Endocrinology 153, 5275-5284
36. Lee, E. K., Jeong, J. U., Chang, J. W., Yang, W. S., Kim, S. B., Park, S. K., Park, J. S., and Lee, S. K. (2012) Activation of AMP-activated protein kinase inhibits albumin-induced endoplasmic reticulum stress and apoptosis through inhibition of reactive oxygen species. Nephron Exp. Nephrol. 121, e38-e48
37. Mayer, C. M., and Belsham, D. D. (2010) Palmitate attenuates insulin signaling and induces endoplasmic reticulum stress and apoptosis in hypothalamic neurons: rescue of resistance and apoptosis through adenosine 5′-monophosphate-activated protein kinase activation. Endocrinology 151, 576-585
38. Terai, K., Hiramoto, Y., Masaki, M., Sugiyama, S., Kuroda, T., Hori, M., Kawase, I., and Hirota, H. (2005) AMP-activated protein kinase protects cardiomyocytes against hypoxic injury through attenuation of endoplasmic reticulum stress. Mol. Cell. Biol. 25, 9554-9575
39. Gomez, E., Powell, M. L., Bevington, A., and Herbert, T. P. (2008) A decrease in cellular energy status stimulates PERK-dependent eIF2α phosphorylation and regulates protein synthesis in pancreaticβ-cells. Biochem. J. 410, 485-493
40. Bertolotti, A., Zhang, Y., Hendershot, L. M., Harding, H. P., and Ron, D. (2000) Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nat. Cell Biol. 2, 326-332
41. Heishi, M., Hayashi, K., Ichihara, J., Ishikawa, H., Kawamura, T., Kanaoka, M., Taiji, M., and Kimura, T. (2008) Comparison of gene expression changes induced by biguanides in db/db mice liver. J. Toxicol. Sci. 33, 339-347
42. Puthalakath, H., O'Reilly, L. A., Gunn, P., Lee, L., Kelly, P. N., Huntington, N. D., Hughes, P. D., Michalak, E. M., McKimm-Breschkin, J., Motoyama, N., Gotoh, T., Akira, S., Bouillet, P., and Strasser, A. (2007) ER stress triggers apoptosis by activating BH3-only protein Bim. Cell 129, 1337-1349
43. Lin, J. H., Li, H., Yasumura, D., Cohen, H. R., Zhang, C., Panning, B., Shokat, K. M., Lavail, M. M., and Walter, P. (2007) IRE1 signaling affects cell fate during the unfolded protein response. Science 318, 944-949
44. Lin, J. H., Li, H., Zhang, Y., Ron, D., and Walter, P. (2009) Divergent effects of PERK and IRE1 signaling on cell viability. PLoS ONE 4, e4170
45. Hetz, C. (2012) The unfolded protein response: controlling cell fate decisions under ER stress and beyond. Nat. Rev. Mol. Cell Biol. 13, 89-102
46. Allagnat, F., Christulia, F., Ortis, F., Pirot, P., Lortz, S., Lenzen, S., Eizirik, D. L., and Cardozo, A. K. (2010) Sustained production of spliced X-box binding protein 1 (XBP1) induces pancreatic beta cell dysfunction and apoptosis. Diabetologia 53, 1120-1130
47. Zeng, L., Zampetaki, A., Margariti, A., Pepe, A. E., Alam, S., Martin, D., Xiao, Q., Wang, W., Jin, Z. G., Cockerill, G., Mori, K., Li, Y. S., Hu, Y., Chien, S., and Xu, Q. (2009) Sustained activation of XBP1 splicing leads to endothelial apoptosis and atherosclerosis development in response to disturbed flow. Proc. Natl. Acad. Sci. U.S.A. 106, 8326-8331
48. Quentin, T., Steinmetz, M., Poppe, A., and Thoms, S. (2012) Metformin differentially activates ER stress signaling pathways without inducing apoptosis. Dis. Model. Mech. 5, 259-269
49. Assan, R., Heuclin, C., Girard, J. R., LeMaire, F., and Attali, J. R. (1975) Phenformin-induced lactic acidosis in diabetic patients. Diabetes 24, 791-800
50. Appleyard, M. V., Murray, K. E., Coates, P. J., Wullschleger, S., Bray, S. E., Kernohan, N. M., Fleming, S., Alessi, D. R., and Thompson, A. M. (2012) Phenformin as prophylaxis and therapy in breast cancer xenografts. Br. J. Cancer 106, 1117-1122
51. Caraci, F., Chisari, M., Frasca, G., Chiechio, S., Salomone, S., Pinto, A., Sortino, M. A., and Bianchi, A. (2003) Effects of phenformin on the proliferation of human tumor cell lines. Life Sci. 74, 643-650
52. Appenzeller-Herzog, C., and Hall, M. N. (2012) Bidirectional crosstalk between endoplasmic reticulum stress and mTOR signaling. Trends Cell Biol. 22, 274-282
53. Meares, G. P., Hughes, K. J., Naatz, A., Papa, F. R., Urano, F., Hansen, P. A., Benveniste, E. N., and Corbett, J. A. (2011) IRE1-dependent activation of AMPK in response to nitric oxide. Mol. Cell. Biol. 31, 4286-4297
54. Qin, L., Wang, Z., Tao, L., and Wang, Y. (2010) ER stress negatively regulates AKT/TSC/mTOR pathway to enhance autophagy. Autophagy 6, 239-247