Lipocalin-2 induces cardiomyocyte apoptosis by increasing intracellular iron accumulation

Journal of Biological Chemistry

Volumn 287, Issue 7, 2012, Pages 4808-4817

  Xu, Guoxiong ^a   Ahn, JinHee ^a   Chang, SoYoung ^a   Eguchi, Megumi ^a,e   Ogier, Arnaud ^b   Han, SungJun ^b   Park, YoungSam ^b   Shim, ChiYoung ^c   Jang, YangSoo ^c   Yang, Bo ^d   Xu, Aimin ^d   Wang, Yu ^d   Sweeney, Gary ^a,e  

^a Institute Pasteur Korea   (South Korea)

^b Institut Pasteur Korea   (South Korea)

^c Yonsei University College of Medicine   (South Korea)

^d UNIVERSITY OF HONG KONG   (Hong Kong)

^e YORK UNIVERSITY   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ACUTE INFLAMMATORY RESPONSE; ANNEXINS; BAX TRANSLOCATION; CARDIAC REMODELING; CARDIOMYOCYTES; CASPASE-3; COLOCALIZATION; DNA FRAGMENTATION; ENZYMATIC ASSAY; FLUORESCENT PROBES; FUNCTIONAL PARAMETERS; HEART FAILURE; INSULIN RESISTANCE; INTRACELLULAR IRON; IRON CHELATORS; MITOCHONDRIAL MEMBRANE POTENTIAL; NEONATAL RAT CARDIOMYOCYTES; PHOSPHATIDYLSERINE; PROAPOPTOTIC PROTEIN BAX; PROINFLAMMATORY; TRANSIENT TRANSFECTION; TUNEL ASSAY; WESTERN BLOTTING;

CARDIOLOGY; FLOW CYTOMETRY; IRON; MITOCHONDRIA;

CELL DEATH;

CASPASE 3; DNA; DYE; GREEN FLUORESCENT PROTEIN; IRON; LIPOCORTIN 5; NEUTROPHIL GELATINASE ASSOCIATED LIPOCALIN; PHOSPHATIDYLSERINE; PROTEIN BAX; RECOMBINANT PROTEIN;

ANIMAL CELL; APOPTOSIS; ARTICLE; CARDIOVASCULAR PARAMETERS; CONTROLLED STUDY; DNA FRAGMENTATION; ENZYME ACTIVITY; ENZYME ASSAY; ENZYME DEGRADATION; FLOW CYTOMETRY; GENETIC TRANSFECTION; HEART MUSCLE CELL; IMMUNOFLUORESCENCE TEST; MITOCHONDRIAL MEMBRANE POTENTIAL; MITOCHONDRION; MOUSE; NEWBORN; NICK END LABELING; NONHUMAN; PRIORITY JOURNAL; PROTEIN LOCALIZATION; RAT; WESTERN BLOTTING;

ACUTE-PHASE PROTEINS; ANIMALS; ANNEXIN A5; APOPTOSIS; BCL-2-ASSOCIATED X PROTEIN; BLOTTING, WESTERN; CASPASE 3; CELL LINE; DNA FRAGMENTATION; IN SITU NICK-END LABELING; IRON; LIPOCALINS; MICE; MYOCYTES, CARDIAC; ONCOGENE PROTEINS; PHOSPHATIDYLSERINES; PROTEIN TRANSPORT; RATS;

MUS; RATTUS;

EID: 84863127635     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M111.275719     Document Type: Article

References (60)

1. Mazzone, T., Chait, A., and Plutzky, J. (2008) Cardiovascular disease risk in type 2 diabetes mellitus: insights from mechanistic studies. Lancet 371, 1800-1809 (Pubitemid 351697956)
2. Trivedi, P. S., and Barouch, L. A. (2008) Cardiomyocyte apoptosis in animal models of obesity. Curr. Hypertens. Rep. 10, 454-460
3. Walsh, K. (2009) Adipokines, myokines and cardiovascular disease. Circ. J. 73, 13-18
4. Artham, S. M., Lavie, C. J., Patel, H. M., and Ventura, H. O. (2008) Impact of obesity on the risk of heart failure and its prognosis. J. Cardiometab. Syndr. 3, 155-161
5. Abel, E. D., Litwin, S. E., and Sweeney, G. (2008) Cardiac remodeling in obesity. Physiol. Rev. 88, 389-419 (Pubitemid 351520084)
6. Schwartz, N., Michaelson, J. S., and Putterman, C. (2007) Lipocalin-2, TWEAK, and other cytokines as urinary biomarkers for lupus nephritis. Ann. N.Y. Acad. Sci. 1109, 265-274 (Pubitemid 47511369)
7. Kjeldsen, L., Johnsen, A. H., Sengeløv, H., and Borregaard, N. (1993) Isolation and primary structure of NGAL, a novel protein associated with human neutrophil gelatinase. J. Biol. Chem. 268, 10425-10432 (Pubitemid 23150227)
8. Flower, D. R. (1996) The lipocalin protein family: structure and function. Biochem. J. 318, 1-14
9. Cowland, J. B., and Borregaard, N. (1997) Molecular characterization and pattern of tissue expression of the gene for neutrophil gelatinase-associated lipocalin from humans. Genomics 45, 17-23 (Pubitemid 27449379)
10. Jang, Y., Lee, J., Wang, Y., and Sweeney, G. (2011) Emerging clinical and experimental evidence for the role of lipocalin-2 in metabolic syndrome. Clin. Exp. Physiol. Pharmacol., in press
11. Wang, Y., Lam, K. S., Kraegen, E. W., Sweeney, G., Zhang, J., Tso, A. W., Chow, W. S., Wat, N. M., Xu, J. Y., Hoo, R. L., and Xu, A. (2007) Lipocalin-2 is an inflammatory marker closely associated with obesity, insulin resistance, and hyperglycemia in humans. Clin. Chem. 53, 34-41 (Pubitemid 46047761)
12. Choi, K. M., Lee, J. S., Kim, E. J., Baik, S. H., Seo, H. S., Choi, D. S., Oh, D. J., and Park, C. G. (2008) Implication of lipocalin-2 and visfatin levels in patients with coronary heart disease. Eur. J. Endocrinol. 158, 203-207 (Pubitemid 351298537)
13. Law, I. K., Xu, A., Lam, K. S., Berger, T., Mak, T. W., Vanhoutte, P. M., Liu, J. T., Sweeney, G., Zhou, M., Yang, B., and Wang, Y. (2010) Lipocalin-2 deficiency attenuates insulin resistance associated with aging and obesity. Diabetes 59, 872-882
14. Guo, H., Jin, D., Zhang, Y., Wright, W., Bazuine, M., Brockman, D. A., Bernlohr, D. A., and Chen, X. (2010) Lipocalin-2 deficiency impairs thermogenesis and potentiates diet-induced insulin resistance in mice. Diabetes 59, 1376-1385
15. Yan, Q. W., Yang, Q., Mody, N., Graham, T. E., Hsu, C. H., Xu, Z., Houstis, N. E., Kahn, B. B., and Rosen, E. D. (2007) The adipokine lipocalin 2 is regulated by obesity and promotes insulin resistance. Diabetes 56, 2533-2540 (Pubitemid 47523260)
16. van Dam, R. M., and Hu, F. B. (2007) Lipocalins and insulin resistance: etiological role of retinol-binding protein 4 and lipocalin-2? Clin. Chem. 53, 5-7
17. Damman, K., van Veldhuisen, D. J., Navis, G., Voors, A. A., and Hillege, H. L. (2008) Urinary neutrophil gelatinase-associated lipocalin (NGAL), a marker of tubular damage, is increased in patients with chronic heart failure. Eur. J. Heart Fail. 10, 997-1000
18. Bolignano, D., Basile, G., Parisi, P., Coppolino, G., Nicocia, G., and Buemi, M. (2009) Increased plasma neutrophil gelatinase-associated lipocalin levels predict mortality in elderly patients with chronic heart failure. Rejuvenation Res. 12, 7-14
19. Poniatowski, B., Malyszko, J., Bachorzewska-Gajewska, H., Malyszko, J. S., and Dobrzycki, S. (2009) Serum neutrophil gelatinase-associated lipocalin as a marker of renal function in patients with chronic heart failure and coronary artery disease. Kidney Blood Press. Res. 32, 77-80
20. Yndestad, A., Landrø, L., Ueland, T., Dahl, C. P., Flo, T. H., Vinge, L. E., Espevik, T., Frøland, S. S., Husberg, C., Christensen, G., Dickstein, K., Kjekshus, J., Øie, E., Gullestad, L., and Aukrust, P. (2009) Increased systemic and myocardial expression of neutrophil gelatinase-associated lipocalin in clinical and experimental heart failure. Eur. Heart J. 30, 1229-1236
21. Hemdahl, A. L., Gabrielsen, A., Zhu, C., Eriksson, P., Hedin, U., Kastrup, J., Thorén, P., and Hansson, G. K. (2006) Expression of neutrophil gelatinase-associated lipocalin in atherosclerosis and myocardial infarction. Arterioscler. Thromb. Vasc. Biol. 26, 136-142 (Pubitemid 43732240)
22. Bu, D. X., Hemdahl, A. L., Gabrielsen, A., Fuxe, J., Zhu, C., Eriksson, P., and Yan, Z. Q. (2006) Induction of neutrophil gelatinase-associated lipocalin in vascular injury via activation of nuclear factor-κB. Am. J. Pathol. 169, 2245-2253 (Pubitemid 351181982)
23. Aigner, F., Maier, H. T., Schwelberger, H. G., Wallnöfer, E. A., Amberger, A., Obrist, P., Berger, T., Mak, T. W., Maglione, M., Margreiter, R., Schneeberger, S., and Troppmair, J. (2007) Lipocalin-2 regulates the inflammatory response during ischemia and reperfusion of the transplanted heart. Am. J. Transplant. 7, 779-788 (Pubitemid 46481201)
24. Olivetti, G., Abbi, R., Quaini, F., Kajstura, J., Cheng, W., Nitahara, J. A., Quaini, E., Di Loreto, C., Beltrami, C. A., Krajewski, S., Reed, J. C., and Anversa, P. (1997) Apoptosis in the failing human heart. N. Engl. J. Med. 336, 1131-1141
25. Takemura, G., and Fujiwara, H. (2004) Role of apoptosis in remodeling after myocardial infarction. Pharmacol. Ther. 104, 1-16 (Pubitemid 39410559)
26. Narula, J., Haider, N., Virmani, R., DiSalvo, T. G., Kolodgie, F. D., Hajjar, R. J., Schmidt, U., Semigran, M. J., Dec, G. W., and Khaw, B. A. (1996) Apoptosis in myocytes in end-stage heart failure. N. Engl. J. Med. 335, 1182-1189 (Pubitemid 26339772)
27. Narula, J., Kolodgie, F. D., and Virmani, R. (2000) Apoptosis and cardiomyopathy. Curr. Opin. Cardiol. 15, 183-188 (Pubitemid 30326641)
28. Devireddy, L. R., Teodoro, J. G., Richard, F. A., and Green, M. R. (2001) Induction of apoptosis by a secreted lipocalin that is transcriptionally regulated by IL-3 deprivation. Science 293, 829-834 (Pubitemid 32743967)
29. Lee, S., Park, J. Y., Lee, W. H., Kim, H., Park, H. C., Mori, K., and Suk, K. (2009) Lipocalin-2 is an autocrine mediator of reactive astrocytosis. J. Neurosci. 29, 234-249
30. Bong, J. J., Seol, M. B., Kim, H. H., Han, O., Back, K., and Baik, M. (2004) The 24p3 gene is induced during involution of the mammary gland and induces apoptosis of mammary epithelial cells. Mol. Cell 17, 29-34 (Pubitemid 39137040)
31. Zheng, L. T., Lee, S., Yin, G. N., Mori, K., and Suk, K. (2009) Downregulation of lipocalin 2 contributes to chemoresistance in glioblastoma cells. J. Neurochem. 111, 1238-1251
32. Kooncumchoo, P., Sharma, S., Porter, J., Govitrapong, P., and Ebadi, M. (2006) Coenzyme Q(10) provides neuroprotection in iron-induced apoptosis in dopaminergic neurons. J. Mol. Neurosci. 28, 125-141
33. Velez-Pardo, C., Jimenez Del Rio, M., Verschueren, H., Ebinger, G., and Vauquelin, G. (1997) Dopamine and iron induce apoptosis in PC12 cells. Pharmacol. Toxicol. 80, 76-84 (Pubitemid 27078230)
34. Devireddy, L. R., Gazin, C., Zhu, X., and Green, M. R. (2005) A cell-surface receptor for lipocalin 24p3 selectively mediates apoptosis and iron uptake. Cell 123, 1293-1305 (Pubitemid 41821786)
35. Oudit, G. Y., Trivieri, M. G., Khaper, N., Husain, T., Wilson, G. J., Liu, P., Sole, M. J., and Backx, P. H. (2004) Taurine supplementation reduces oxidative stress and improves cardiovascular function in an iron-overload murine model. Circulation 109, 1877-1885 (Pubitemid 38509123)
36. Whittaker, P., Hines, F. A., Robl, M. G., and Dunkel, V. C. (1996) Histopathological evaluation of liver, pancreas, spleen, and heart from iron-overloaded Sprague-Dawley rats. Toxicol. Pathol. 24, 558-563 (Pubitemid 26374759)
37. Arvapalli, R. K., Paturi, S., Laurino, J. P., Katta, A., Kakarla, S. K., Gadde, M. K., Wu, M., Rice, K. M., Walker, E. M., Wehner, P., and Blough, E. R. (2010) Deferasirox decreases age-associated iron accumulation in the aging F344XBN rat heart and liver. Cardiovasc. Toxicol. 10, 108-116
38. Wang, Y., Wu, M., Al-Rousan, R., Liu, H., Fannin, J., Paturi, S., Arvapalli, R. K., Katta, A., Kakarla, S. K., Rice, K. M., Triest, W. E., and Blough, E. R. (2011) Iron-induced cardiac damage: role of apoptosis and deferasirox intervention. J. Pharmacol. Exp. Ther. 336, 56-63
39. Kohgo, Y., Ikuta, K., Ohtake, T., Torimoto, Y., and Kato, J. (2008) Body iron metabolism and pathophysiology of iron overload. Int. J. Hematol. 88, 7-15
40. Bachman, M. A., Miller, V. L., and Weiser, J. N. (2009) Mucosal lipocalin 2 has proinflammatory and iron-sequestering effects in response to bacterial enterobactin. PLoS Pathog. 5, e1000622
41. Schmidt-Ott, K. M., Mori, K., Kalandadze, A., Li, J. Y., Paragas, N., Nicholas, T., Devarajan, P., and Barasch, J. (2006) Neutrophil gelatinase-associated lipocalin-mediated iron traffic in kidney epithelia. Curr. Opin. Nephrol. Hypertens. 15, 442-449 (Pubitemid 44297988)
42. Goetz, D. H., Holmes, M. A., Borregaard, N., Bluhm, M. E., Raymond, K. N., and Strong, R. K. (2002) The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition. Mol. Cell 10, 1033-1043 (Pubitemid 36001971)
43. Yang, J., Goetz, D., Li, J. Y., Wang, W., Mori, K., Setlik, D., Du, T., Erdjument-Bromage, H., Tempst, P., Strong, R., and Barasch, J. (2002) An iron delivery pathway mediated by a lipocalin. Mol. Cell 10, 1045-1056 (Pubitemid 35453824)
44. Palanivel, R., Fang, X., Park, M., Eguchi, M., Pallan, S., De Girolamo, S., Liu, Y., Wang, Y., Xu, A., and Sweeney, G. (2007) Globular and full-length forms of adiponectin mediate specific changes in glucose and fatty acid uptake and metabolism in cardiomyocytes. Cardiovasc. Res. 75, 148-157 (Pubitemid 46873521)
45. Deleted in proof
46. Xu, G., Zhou, H., Wang, Q., Auersperg, N., and Peng, C. (2006) Activin receptor-like kinase 7 induces apoptosis through up-regulation of Bax and down-regulation of Xiap in normal and malignant ovarian epithelial cell lines. Mol. Cancer Res. 4, 235-246
47. Deleted in proof
48. Hou, Q., and Hsu, Y. T. (2005) Bax translocates from cytosol to mitochondria in cardiac cells during apoptosis: development of a GFP-Bax-stable H9c2 cell line for apoptosis analysis. Am. J. Physiol. Heart Circ. Physiol. 289, H477-487 (Pubitemid 40934135)
49. Petrat, F., Rauen, U., and de Groot, H. (1999) Determination of the chelatable iron pool of isolated rat hepatocytes by digital fluorescence microscopy using the fluorescent probe, phen green SK. Hepatology 29, 1171-1179 (Pubitemid 29168752)
50. Shin, E. J., Schram, K., Zheng, X. L., and Sweeney, G. (2009) Leptin attenuates hypoxia/reoxygenation-induced activation of the intrinsic pathway of apoptosis in rat H9c2 cells. J. Cell. Physiol. 221, 490-497
51. Mishra, J., Dent, C., Tarabishi, R., Mitsnefes, M. M., Ma, Q., Kelly, C., Ruff, S. M., Zahedi, K., Shao, M., Bean, J., Mori, K., Barasch, J., and Devarajan, P. (2005) Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 365, 1231-1238 (Pubitemid 40469655)
52. Flo, T. H., Smith, K. D., Sato, S., Rodriguez, D. J., Holmes, M. A., Strong, R. K., Akira, S., and Aderem, A. (2004) Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Nature 432, 917-921 (Pubitemid 40037155)
53. Chan, Y. R., Liu, J. S., Pociask, D. A., Zheng, M., Mietzner, T. A., Berger, T., Mak, T. W., Clifton, M. C., Strong, R. K., Ray, P., and Kolls, J. K. (2009) Lipocalin 2 is required for pulmonary host defense against Klebsiella infection. J. Immunol. 182, 4947-4956
54. Munoz, J. P., Chiong, M., García, L., Troncoso, R., Toro, B., Pedrozo, Z., Diaz-Elizondo, J., Salas, D., Parra, V., Núñez, M. T., Hidalgo, C., and Lavandero, S. (2010) Iron induces protection and necrosis in cultured cardiomyocytes: role of reactive oxygen species and nitric oxide. Free Radic. Biol. Med. 48, 526-534
55. Spagnuolo, R. D., Recalcati, S., Tacchini, L., and Cairo, G. (2011) Role of hypoxia-inducible factors in the dexrazoxane-mediated protection of cardiomyocytes from doxorubicin-induced toxicity. Br. J. Pharmacol. 163, 299-312
56. Kahn, E., Baarine, M., Pelloux, S., Riedinger, J. M., Frouin, F., Tourneur, Y., and Lizard, G. (2010) Iron nanoparticles increase 7-ketocholesterol-induced cell death, inflammation, and oxidation on murine cardiac HL1-NB cells. Int. J. Nanomedicine 5, 185-195
57. Goswami, T., Rolfs, A., and Hediger, M. A. (2002) Iron transport: emerging roles in health and disease. Biochem. Cell Biol. 80, 679-689 (Pubitemid 36124826)
58. Deleted in proof
59. Hvidberg, V., Jacobsen, C., Strong, R. K., Cowland, J. B., Moestrup, S. K., and Borregaard, N. (2005) The endocytic receptor megalin binds the iron transporting neutrophil-gelatinase-associated lipocalin with high affinity and mediates its cellular uptake. FEBS Lett. 579, 773-777
60. Borgna-Pignatti, C., Cappellini, M. D., De Stefano, P., Del Vecchio, G. C., Forni, G. L., Gamberini, M. R., Ghilardi, R., Piga, A., Romeo, M. A., Zhao, H., and Cnaan, A. (2006) Cardiac morbidity and mortality in deferoxamine- or deferiprone-treated patients with thalassemia major. Blood 107, 3733-3737