Targeted disruption of NFATc3, but not NFATc4, reveals an intrinsic defect in calcineurin-mediated cardiac hypertrophic growth

Molecular and Cellular Biology

Volumn 22, Issue 21, 2002, Pages 7603-7613

  Wilkins, Benjamin J ^a   De Windt, Leon J ^a   Bueno, Orlando F ^a   Braz, Julian C ^a   Glascock, Betty J ^a   Kimball, Thomas F ^a   Molkentin, Jeffery D ^a  

^a CINCINNATI CHILDREN'S HOSPITAL MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANGIOTENSIN; CALCINEURIN; CALCIUM; TRANSCRIPTION FACTOR NFAT; TRANSCRIPTION FACTOR NFATC3; TRANSCRIPTION FACTOR NFATC4; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CALCIUM CELL LEVEL; CONTROLLED STUDY; GENE TARGETING; HEART HYPERTROPHY; IN VIVO STUDY; MOUSE; NONHUMAN; NULL ALLELE; PRIORITY JOURNAL; REGULATORY MECHANISM; SIGNAL TRANSDUCTION; TRANSCRIPTION REGULATION; TRANSGENE;

ANGIOTENSIN II; ANIMALS; BLOTTING, WESTERN; CALCINEURIN; CELL DIVISION; CELL NUCLEUS; DNA-BINDING PROTEINS; FEMALE; GENE TARGETING; HYPERTROPHY; MALE; MICE; MODELS, GENETIC; MUTAGENESIS; MUTAGENESIS, SITE-DIRECTED; MYOCARDIUM; NFATC TRANSCRIPTION FACTORS; PROTEIN ISOFORMS; RATS; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RNA, MESSENGER; TIME FACTORS; TRANSCRIPTION FACTORS; TRANSGENES;

ANIMALIA;

EID: 0036837672     PISSN: 02707306     EISSN: None     Source Type: Journal    
DOI: 10.1128/MCB.22.21.7603-7613.2002     Document Type: Article

References (72)

1. Antos, C. L., T. A. McKinsey, N. Frey, W. Kutschke, J. McAnally, J. M. Shelton, J. A. Richardson, J. A. Hill, and E. N. Olson. 2002. Activated glycogen synthase-3β suppresses cardiac hypertrophy in vivo. Proc. Natl. Acad. Sci. USA 99:907-912.
2. Beals, C. R., C. M. Sheridan, C. W. Turck, P. Gardner, and G. R. Crabtree. 1997. Nuclear export of NF-ATc enhanced by glycogen synthase kinase-3. Science 275:1930-1934.
3. 2+-dependent gene expression mediated by MEF2 transcription factors. J. Biol. Chem. 275:197-209.
4. Bueno, O. F., B. J. Wilkins, K. M. Tymitz, B. J. Glascock, T. F. Kimball, J. N. Lorenz, and J. D. Molkentin. 2002. Impaired cardiac hypertrophic response in calcineurin Aβ-deficient mice. Proc. Natl. Acad. Sci. USA 99:4586-4591.
5. 2+, calcineurin, and NF-AT. Cell 96:611-614.
6. de la Pompa, J. L, L. A. Timmerman, H. Takimoto, H. Yoshida, A. J. Elia, E. Samper, J. Potter, A. Wakeham, L. Marengere, B. L. Langille, G. R. Crabtree, and T. W. Mak. 1998. Role of the NF-ATc transcription factor in morphogenesis of cardiac valves and septum. Nature 392:182-186.
7. De Windt, L. J,. H. W. Lim, O. F. Bueno, Q. Liang, J. C. Braz, B. J. Glascock, T. F. Kimball, F. del Monte, R. J. Hajjar, and J. D. Molkentin. 2001. Targeted inhibition of calcineurin attenuates cardiac hypertrophy invivo. Proc. Natl. Acad. Sci. USA 98:3322-3327.
8. 2-terminal kinase activation in the heart: cross-talk between cardiac hypertrophic signaling pathways. J. Biol. Chem. 275:13571-13579.
9. Deng, L., B. Huang, D. Qin, K. Ganguly, and N. El-Sherif. 2001. Calcineurin inhibition ameliorates structural, contractile, and electrophysiologic consequences of postinfarction remodeling. J. Cardiovasc. Electrophysiol. 12:1055-1061.
10. Ding, B., R. L. Price, T. K. Borg, E. O. Weinberg, P. F. Halloran, and B. H. Lorell. 1999. Pressure overload induces severe hypertrophy in mice treated with cyclosporine, an inhibitor of calcineurin. Circ. Res. 84:729-734.
11. Eto, Y., K. Yonekura, M. Sonoda, N. Arai, M. Sata, S. Sugiura, K. Takenaka, A. Gualberto, M. L. Hixon, M. W. Wagner, and T. Aoyagi. 2000. Calcineurin is activated in rat hearts with physiological left ventricular hypertrophy induced by voluntary exercise training. Circulation 101:2134-2137.
12. 2+ response in mutant sarcomere protein-mediated familial hypertrophic cardiomyopathy. J. Clin. Investig. 106:1351-1359.
13. Flanagan, W. M., B. Corthesy, R. J. Bram, and G. R. Crabtree. 1991. Nuclear association of a T-cell transcription factor blocked by FK506 and cyclosporin A. Nature 352:803-807.
14. Goldspink, P. H., R. D. McKinney, V. A. Kimball, D. L. Geenen, and P. M. Buttrick. 2001. Angiotensin II induced cardiac hypertrophy in vivo is inhibited by cyclosporin A in adult rats. Mol. Cell. Biochem. 226:83-88.
15. 2+/calcineurin and NFATc3/c4 pattern the developing vasculature. Cell 105:863-875.
16. Haq, S., G. Choukroun, Z. B. Kang, H. Ranu, T. Matsui, A. Rosenzweig, J. D. Molkentin, A. Alessandrini, J. Woodgett, R. Hajjar, A. Michael, and T. Force. 2000. Glycogen synthase kinase-3β is a negative regulator of cardiomyocyte hypertrophy. J. Cell Biol. 151:117-130.
17. Hill, J. A., B. Rothermel, K. D. Yoo, B. Cabuay, E. Demetroulis, R. M. Weiss, W. Kutschke, R. Bassel-Duby, and R. S. Williams. 2002. Targeted inhibition of calcineurin in pressure-overload cardiac hypertrophy: preservation of systolic function. J. Biol. Chem. 277:10251-10255
18. Hill, J. A., M. Karimi, W. Kutschke, R. L. Davisson, K. Zimmerman, Z. Wang, R. E. Kerber, and R. M. Weiss. 2000. Cardiac hypertrophy is not a required compensatory response to short-term pressure overload. Circulation 101:2863-2869.
19. Hodge, M. R., A. M. Ranger, F. C. de la Brousse, T. Hoey, M. J. Grusby, and L. H. Glimcher. 1996. Hyperproliferation and dysregulation of IL-4 expression in NF-ATp-deficient mice. Immunity 4:397-405.
20. Hoey, T., Y. L. Sun, K. Williamson, and X. Xu. 1995. Isolation of two new members of the NF-AT gene family and functional characterization of the NF-AT proteins. Immunity 2:461-472.
21. Horsley, V., B. B. Friday, S. Matteson, K. M. Kegley, J. Gephart, and G. Pavlath. 2001. Regulation of the growth of multinucleated muscle cells by an NFATc2-dependent pathway. J. Cell Biol. 153:329-338.
22. Janssen, P. M., O. Zeitz, B. Keweloh, U. Siegel, L. S. Maier, P. Barckhausen, B. Pieske, J. Prestle, S. E. Lehnart, and G. Hasenfuss. 2000. Influence of cyclosporine A on contractile function, calcium handling, and energetics is isolated human and rabbit myocardium. Cardiovasc. Res. 47:99-107.
23. Jones, W. K., I. L. Grupp, T. Doetschman, G. Grupp, H. Osinska, T. E. Hewett, G. Boivin, J. Gulick, W. A. Ng, and J. Robbins. 1996. Ablation of the murine alpha myosin heavy chain gene leads to dosage effects and functional deficits in the heart. J. Clin. Investig. 98:1906-1917.
24. Kamiya, H., K. Okumura, M. Ito, Y. Saburi, T. Tomida, K. Hayashi, H. Matsui, and T. Hayakawa. 2001. Calcineurin inhibitor attenuates cardiac hypertrophy due to energy metabolic disorder. Can. J. Cardiol. 17:1292-1298.
25. -/- mice leads to decreased muscle size in the adult. Dev. Biol. 232:115-126.
26. Liew, C. C., G. Jackowski, T. Ma, and M. J. Sole. 1983. Nonenzymatic separation of myocarial cell nuclei from whole heart tissue. Am. J. Physiol. 244:C3-C10.
27. Lim, H. W., L. J. De Windt, L. Steinberg, T. Taigen, S. A. Witt, T. R. Kimball, and J. D. Molkentin. 2000. Calcineurin expression, activation, and function in cardiac pressure-overload hypertrophy. Circulation 101:2431-2437.
28. Liu, J., N. Koyano-Nakagawa, Y. Amasaki, F. Saito-Ohara, T. Ikeuchi, S. Imai, T. Takano, N. Arai, T. Yokota, and K. Arai. 1997. Calcineurin-dependent nuclear translocation of a murine transcription factor NFATx: molecular cloning and functional characterization. Mol. Biol. Cell 8:157-170.
29. Lop6z-Rodriguez, C., J. Aramburu, A. S. Rakeman, and A. Rao. 1999. NFAT5, a constitutively nuclear NFAT protein that does not cooperate with Fos and Jun. Proc. Natl. Acad. Sci. USA 96:7214-7219.
30. Lorell, B. H., and B. A. Carabello. 2000. Left ventricular hypertrophy: pathogenesis, detection, and prognosis. Circulation 102:470-479.
31. Luo, Z., K. G. Shyu, A. Gualberto, and K. Walsh. 1998. Calcineurin and cardiac hypertrophy. Nat. Med. 10:1092-1093.
32. Mao, Z., and M. Wiedmann. 1999. Calcineurin enhances MEF2 DNA binding activity in calcium-dependent survival of cerebellar granule neurons. J. Biol. Chem. 274:31102-31107.
33. Masuda, E. S., Y. Naito, H. Tokumitsu, D. Campbell, F. Saito, C. Hannum, K. Arai, and N. Arai. 1995. NFATx, a novel member of the nuclear factor of activated T cells family that is expressed predominantly in the thymus. Mol. Cell. Biol. 15:2697-2706.
34. Meguro, T., C. Hong, K. Asai, G. Takagi, M. T. A. cKinsey, E. N. Olson, and S. F. Vatner. 1999. Cyclosporine attenuates pressure-overload hypertrophy in mice while enhancing susceptibility to decompensation and heart failure. Circ. Res. 84:735-740.
35. Mende, U., A. Kagen, A. Cohen, J. Aramburu, F. J. Schoen, and E. J. Neer. 1998. Transient cardiac expression of constitutively active Gαq leads to hypertrophy and dilated cardiomyopathy by calcineurin-dependent and independent pathways. Proc. Natl. Acad. Sci. USA 95:13893-13898.
36. Mervaala, E., D. N. Muller, J. K. Park, R. Dechend, F. Schmidt, A. Fiebeler, M. Bieringer, V. Breu, D. Ganten, H. Haller, and F. C. Luft. 2000. Cyclosporin A protects against angiotensin II-induced end-organ damage in double transgenic rats harboring human renin and angiotensinogen genes. Hypertension 35(Pt. 2):360-366.
37. Meyer, S., N. G. Kohler, and A. Joly. 1997. Cyclosporine A is an uncompetitive inhibitor of proteasome activity and prevents NF-κB activation. FEBS Lett. 413:354-358.
38. Molkentin, J. D., Q. Lin, S. A. Duncan, and E. N. Olson. 1997. Requirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis. Genes Dev. 11:1061-1072.
39. Molkentin, J. D. 2000. Calcineurin and beyond: cardiac hypertrophic signaling. Circ. Res. 87:731-738.
40. Molkentin, J. D., and G. W. Dorn II. 2001. Cytoplasmic signaling pathways that regulate cardiac hypertrophy. Annu. Rev. Physiol. 63:391-426.
41. Molkentin, J. D., J. R. Lu, C. L. Antos, B. Markham, J. Richardson, J. Robbins, S. R. Grant, and E. N. Olson. 1998. A calcineurin-dependent transcriptional pathway for cardiac hypertrophy. Cell 93:215-228.
42. Murat, A., C. Pellieux, H. R. Brunner, and T. Pedrazzini. 2000. Calcineurin blockade prevents cardiac mitogen-activated protein kinase activation and hypertrophy in renovascular hypertension. J. Biol. Chem. 275:40867-40873.
43. Oie, E. B., O. P. Reidar, F. Clausen, and H. Attramadal. 2000. Cyclosporin A inhibits cardiac hypertrophy and enhances cardiac dysfunction during postinfarction failure in rats. Am. J. Physiol. Heart Circ. Physiol. 278:2115-2123.
44. Oukka, M., I. C. Ho, F. C. de la Brousse, T. Hoey, M. J. Grusby, and L. H. Glimeher. 1998. The transcription factor NFAT4 is involved in the generation and survival of T cells. Immunity. 9:295-304.
45. Passier, R., H. Zeng, N. Frey, F. J. Naya, R. L. Nicol, T. A. McKinsey, P. Overbeek, J. A. Richardson, S. R. Grant, and E. N. Olson. 2000. CaM kinase signaling induces cardiac hypertrophy and activates the MEF2 transcription factor in vivo. J. Clin. Investig. 10:1395-1406.
46. Peng, S. L., A. J. Gerth, A. M. Ranger, and L. H. Glimcher. 2001. NFATc1 and NFATc2 together control both T and B cell activation and differentiation. Immunity 14:13-20.
47. Ramirez-Solis, R., R. Davis, and A. Bradley. 1993. Gene targeting in embryonic stem cells. Methods Enzymol. 225:855-878.
48. Ranger, A. M., M. J. Grusby, M. R. Hodge, E. M. Gravallese, F. C. de la Brousse, T. Hoey, C. Mickanin, H. S. Baldwin, and L. H. Glimcher. 1998. The transcription factor NF-ATc is essential for cardiac valve formation. Nature 392:186-190.
49. Ranger, A. M., L. C. Gerstenfeld, J. Wang, T. Kon, H. Bae, E. M. Gravallese, M. J. Glimcher, and L. H. Glimcher. 2000. The nuclear factor of activated T cells (NFAT) transcription factor NFATp (NFATc2) is a repressor of chondrogenesis. J. Exp. Med. 191:9-22.
50. Ranger, A. M., M. Oukka, J. Rengarajan, and L. H. Glimcher. 1998. Inhibitory function of two NFAT family members in lymphoid homeostasis and Th2 development. Immunity 9:627-635.
51. Rao, A., C. Luo, and P. G. Hogan. 1997. Transcription factors of the NFAT family: regulation and function. Annu. Rev. Immunol. 15:707-747.
52. Rothermel, B. A., T. A. McKinsey, R. B. Vega, R. L. Nicol, P. Mammen, J. Yang, C. L. Antos, J. M. Shelton, R. Bassel-Duby, E. N. Olson, and R. S. Williams. 2001. Myocyte-enriched calcineurin-interacting protein, MCIP1, inhibits cardiac hypertrophy in vivo. Proc. Natl. Acad. Sci. USA 98:3328-3333.
53. 2+ influx protects cardiac morphology and ventricular function in K(v)4.2N transgenic mice. Circulation 105:1850-1856.
54. Sakata, Y., T. Masuyama, K. Yamamoto, N. Nishikawa, H. Yamamoto, H. Kondo, K. Ono, K. Otsu, T. Kuzuya, T. Miwa, H. Takeda, E. Miyamoto, and M. Hori. 2000. Calcineurin inhibitor attenuates left ventricular hypertrophy, leading to prevention of heart failure in hypertensive rats. Circulation 102:2269-2275.
55. Shimoyama, M., D. Hayashi, Y. Zou, E. Takimoto, M. Mizukami, K. Monzen, S. Kudoh, Y. Hiroi, Y. Yazaki, R. Nagai, and I. Komuro. 2000. Calcineurin inhibitor attenuates the development and induces the regression of cardiac hypertrophy in rats with salt-sensitive hypertension. Circulation 102:1996-2004.
56. Shimoyama, M., D. Hayashi, E. Takimoto, Y. Zou, T. Oka, H. Uozumi, S. Kudoh, F. Shibasaki, Y. Yazaki, R. Nagai, and I. Komuro. 1999. Calcineurin plays a critical role in pressure overload-induced cardiac hypertrophy. Circulation 100:2449-2454.
57. Shimoyama, M., D. Hayashi, Y. Zou, E. Takimoto, M. Mizukami, K. Monzen, Y. Yazaki, R. Nagai, and I. Komuro. 2001. Calcineurin inhibitor attenuates the development and induces the regression of cardiac hypertrophy in rats with salt-sensitive hypertension. J. Cardiol. 37:114-118.
58. Stroud, J. C., C. Lopez-Rodriguez, A. Rao, and L. Chen. 2002. Structure of a TonEBP-DNA complex reveals DNA encircled by a transcription factor. Nat. Struct. Biol. 9:90-94.
59. Sugimoto, T., S. Stewart, and K. L. Guan. 1997. The calcium-dependent protein phosphatase calcineurin is the major Elk-1 phosphatase. J. Biol. Chem. 272:29415-29418.
60. Sussman, M. A., H. W. Lim, N. Gude, T. Taigen, E. N. Olson, J. Robbins, M. C. Colbert, A. Gualberto, D. F. Wieczorek, and J. D. Molkentin. 1998. Prevention of cardiac hypertrophy in mice by calcineurin inhibition. Science 281:1690-1693.
61. Taigen, T., L. J. De Windt, H. W. Lim, and J. D. Molkentin. 2000. Targeted inhibition of calcineurin prevents agonist-induced cardiomyocyte hypertrophy. Proc. Natl. Acad. Sci. USA 97:1196-1201.
62. Takeda, Y., T. Yoneda, M. Demura, M. Usukura, and H. Mabuchi. 2002. Calcineurin inhibition attenuates mineralocorticoid-induced cardiac hypertrophy. Circulation 105:677-679.
63. Tian, J., and M. Karin. 1999. Stimulation of Elk1 transcriptional activity by mitogen-activated protein kinases is negatively regulated by protein phosphatase 2B (calcineurin). J. Biol. Chem. 274:15173-15180.
64. 2+ exchanger remodeling in pressure overload cardiac hypertrophy. J. Biol. Chem. 276:17706-17711.
65. Wu, H., F. J. Naya, T. A. McKinsey, B. Mercer, J. M. Shelton, E. R. Chin, A. R. Simard, R. N. Michel, R. Bassel-Duby, E. N. Olson, and R. S. Williams. 2000. MEF2 responds to multiple calcium-regulated signals in the control of skeletal muscle fiber-type. EMBO J. 19:1963-1973.
66. Wu, H., B. Rothermel, S. Kanatous, P. Rosenberg, F. J. Naya, J. M. Shelton, K. A. Hutcheson, J. M. DiMaio, E. N. Olson, R. Bassel-Duby, and R. S. Williams. 2001. Activation of MEF2 by muscle activity is mediated through a calcineurin-dependent pathway. EMBO J. 20:6414-6423.
67. Xanthoudakis, S., J. P. Viola, K. T. Shaw, C. Luo, J. D. Wallace, P. T. Bozza, D. C. Luk, T. Curran, and A. Rao. 1996. An enhanced immune response in mice lacking the transcription factor NFAT1. Science 272:892-895.
68. Xia, Y., J. B. McMillin, A. Lewis, M. Moore, W. G. Zhu, R. S. Williams, and R. E. Kellems. 2000. Electrical stimulation of neonatal cardiac myocytes activates the NFAT3 and GATA4 pathways and upregulates the adenylosuccinate synthetase 1 gene. J. Biol. Chem. 275:1855-1863.
69. Yang, G., T. Meguro, C. Hong, K. Asai, G. Takagi, V. L. Karoor, J. Sadoshima, D. E. Vatner, S. P. Bishop, and S. F. Vatner. 2001. Cyclosporine reduces left ventricular mass with chronic aortic banding in mice, which could be due to apoptosis and fibrosis. J. Mol. Cell. Cardiol. 33:1505-1514.
70. Youn, H.-D., T. A. Chatila, and J. O. Liu. 2000. Integration of calcineurin and MEF2 signals by the coactivator p300 during T-cell apoptosis. EMBO J. 19:4323-4331.
71. Zhang, W., R. C. Kowal, F. Rusnak, R. A. Sikkink, E. N. Olson, and R. G. Victor. 1999. Failure of calcineurin inhibitors to prevent pressure-overload left ventricular hypertrophy in rats. Circ. Res. 84:722-728.
72. Zou, Y., Y. Hiroi, H. Uozumi, E. Takimoto, H. Toko, W. Zhu, S. Kudoh, M. Mizukami, M. Shimoyama, F. Shibasaki, and I. Komuro. 2001. Calcineurin plays a critical role in the development of pressure overload-induced cardiac hypertrophy. Circulation 104:97-101.