BRCA2 protein deficiency exaggerates doxorubicin-induced cardiomyocyte apoptosis and cardiac failure

Journal of Biological Chemistry

Volumn 287, Issue 9, 2012, Pages 6604-6614

  Singh, Krishna K ^a,b   Shukla, Praphulla C ^a,b   Quan, Adrian ^a,b   Desjardins, Jean François ^a,b   Lovren, Fina ^a   Pan, Yi ^a   Garg, Vinay ^d   Gosal, Sumandeep ^a,b   Garg, Ankit ^d   Szmitko, Paul E ^c   Schneider, Michael D ^e   Parker, Thomas G ^a,b,c   Stanford, William L ^f   Leong Poi, Howard ^a,b   Teoh, Hwee ^a,b   Al Omran, Mohammed ^b,g   Verma, Subodh ^a,b,c  

^a ST MICHAEL'S HOSPITAL   (Canada)

^b ST MICHAEL'S HOSPITAL   (Canada)

^c UNIVERSITY OF TORONTO   (Canada)

^d QUEEN S UNIVERSITY   (Canada)

^e KING'S COLLEGE LONDON   (United Kingdom)

^f OTTAWA HOSPITAL RESEARCH INSTITUTE   (Canada)

^g KING SAUD UNIVERSITY   (Saudi Arabia)

Author keywords

[No Author keywords available]

Indexed keywords

BREAST CANCER; CARDIAC FUNCTIONS; CARDIOMYOCYTES; CRE-LOXP; CYTOCHROME C; DNA DAMAGES; DOXORUBICIN; KNOCK OUTS; LEFT VENTRICULAR; OVARIAN CANCERS; PHARMACOGENOMIC STUDY; SUSCEPTIBILITY GENES; TUMOR SUPPRESSORS; WILD TYPES;

CHEMOTHERAPY; DISEASES; GENES; HEART; MAMMALS; MICROSCOPIC EXAMINATION;

CELL DEATH;

BRCA2 PROTEIN; CELL DNA; CYTOCHROME C; DOXORUBICIN; PROTEIN BAX; PROTEIN P53; PUMA PROTEIN; RAD51 PROTEIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; CELL FUNCTION; CELL SPECIFICITY; CELL SURVIVAL; CONTROLLED STUDY; DISEASE PREDISPOSITION; DNA DAMAGE; DOUBLE STRANDED DNA BREAK; EMBRYO; ENZYME RELEASE; GENETIC REGULATION; GENOMICS; HEART FAILURE; HEART LEFT VENTRICLE; HEART MUSCLE CELL; HISTOPATHOLOGY; MORTALITY; MOUSE; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN DEPLETION; SINGLE DRUG DOSE; WILD TYPE;

ANIMALS; ANTIBIOTICS, ANTINEOPLASTIC; APOPTOSIS; BRCA2 PROTEIN; DOXORUBICIN; HEART FAILURE; MICE; MICE, KNOCKOUT; MYOCARDIUM; MYOCYTES, CARDIAC; PHENOTYPE; RISK FACTORS; TUMOR SUPPRESSOR PROTEIN P53;

MUS; PYRONIA TITHONUS;

EID: 84857466300     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M111.292664     Document Type: Article

References (52)

1. Rahman, N., and Stratton, M. R. (1998) The genetics of breast cancer susceptibility. Annu. Rev. Genet. 32, 95-121 (Pubitemid 29045309)
2. Kinzler, K. W., and Vogelstein, B. (1997) Cancer-susceptibility genes. Gatekeepers and caretakers. Nature 386, 761-763
3. Chen, P. L., Chen, C. F., Chen, Y., Xiao, J., Sharp, Z. D., and Lee, W. H. (1998) The BRC repeats in BRCA2 are critical for RAD51 binding and resistance to methyl methanesulfonate treatment. Proc. Natl. Acad. Sci. U.S.A. 95, 5287-5292 (Pubitemid 28208590)
4. Yoshida, K., and Miki, Y. (2004) Role of BRCA1 and BRCA2 as regulators of DNA repair, transcription, and cell cycle in response to DNA damage. Cancer Sci. 95, 866-871 (Pubitemid 40045520)
5. Connor, F., Bertwistle, D., Mee, P. J., Ross, G. M., Swift, S., Grigorieva, E., Tybulewicz, V. L., and Ashworth, A. (1997) Tumorigenesis and a DNA repair defect in mice with a truncating Brca2 mutation. Nat. Genet. 17, 423-430
6. Kennedy, R. D., Quinn, J. E., Mullan, P. B., Johnston, P. G., and Harkin, D. P. (2004) The role of BRCA1 in the cellular response to chemotherapy. J. Natl. Cancer Inst. 96, 1659-1668 (Pubitemid 39585635)
7. Lefrak, E. A., Pitha, J., Rosenheim, S., and Gottlieb, J. A. (1973) A clinicopathologic analysis of Adriamycin cardiotoxicity. Cancer 32, 302-314
8. Yoshida, M., Shiojima, I., Ikeda, H., and Komuro, I. (2009) Chronic doxorubicin cardiotoxicity is mediated by oxidative DNA damage-ATM-p53-apoptosis pathway and attenuated by pitavastatin through the inhibition of Rac1 activity. J. Mol. Cell. Cardiol. 47, 698-705
9. Arola, O. J., Saraste, A., Pulkki, K., Kallajoki, M., Parvinen, M., and Voipio-Pulkki, L. M. (2000) Acute doxorubicin cardiotoxicity involves cardiomyocyte apoptosis. Cancer Res. 60, 1789-1792 (Pubitemid 30207630)
10. Minotti, G., Menna, P., Salvatorelli, E., Cairo, G., and Gianni, L. (2004) Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol. Rev. 56, 185-229 (Pubitemid 38720829)
11. Tutt, A., Bertwistle, D., Valentine, J., Gabriel, A., Swift, S., Ross, G., Griffin, C., Thacker, J., and Ashworth, A. (2001) Mutation in Brca2 stimulates error-prone homology-directed repair of DNA double-strand breaks occurring between repeated sequences. EMBO J. 20, 4704-4716 (Pubitemid 32848624)
12. Jonkers, J., Meuwissen, R., van der Gulden, H., Peterse, H., van der Valk, M., and Berns, A. (2001) Synergistic tumor suppressor activity of BRCA2 and p53 in a conditional mouse model for breast cancer. Nat. Genet. 29, 418-425 (Pubitemid 34326692)
13. Agah, R., Frenkel, P. A., French, B. A., Michael, L. H., Overbeek, P. A., and Schneider, M. D. (1997) Gene recombination in postmitotic cells. Targeted expression of Cre recombinase provokes cardiac-restricted, sitespecific rearrangement in adult ventricular muscle in vivo. J. Clin. Investig. 100, 169-179 (Pubitemid 27311255)
14. Hakem, R., de la Pompa, J. L., and Mak, T. W. (1998) Developmental studies of Brca1 and Brca2 knock-out mice. J. Mammary Gland Biol. Neoplasia 3, 431-445 (Pubitemid 128515796)
15. Sauer, B. (1998) Inducible gene targeting in mice using the Cre/lox system. Methods 14, 381-392
16. Buerger, A., Rozhitskaya, O., Sherwood, M. C., Dorfman, A. L., Bisping, E., Abel, E. D., Pu, W. T., Izumo, S., and Jay, P. Y. (2006) Dilated cardiomyopathy resulting from high-level myocardial expression of Cre-recombinase. J. Card. Fail. 12, 392-398 (Pubitemid 43817587)
17. Henderson, I. C., and Frei, E., 3rd (1979) Testing for doxorubicin cardiotoxicity. N. Engl. J. Med. 300, 1393-1394
18. Kang, Y. J., Chen, Y., Yu, A., Voss-McCowan, M., and Epstein, P. N. (1997) Overexpression of metallothionein in the heart of transgenic mice suppresses doxorubicin cardiotoxicity. J. Clin. Investig. 100, 1501-1506 (Pubitemid 27425776)
19. Shizukuda, Y., Matoba, S., Mian, O. Y., Nguyen, T., and Hwang, P. M. (2005) Targeted disruption of p53 attenuates doxorubicin-induced cardiac toxicity in mice. Mol. Cell. Biochem. 273, 25-32 (Pubitemid 40774760)
20. Yen, H. C., Oberley, T. D., Vichitbandha, S., Ho, Y. S., and St Clair, D. K. (1996) The protective role of manganese superoxide dismutase against Adriamycin-induced acute cardiac toxicity in transgenic mice. J. Clin. Investig. 98, 1253-1260 (Pubitemid 26299939)
21. Dickey, J. S., Baird, B. J., Redon, C. E., Sokolov, M. V., Sedelnikova, O. A., and Bonner, W. M. (2009) Intercellular communication of cellular stress monitored by γ-H2AX induction. Carcinogenesis 30, 1686-1695
22. Yuan, S. S., Lee, S. Y., Chen, G., Song, M., Tomlinson, G. E., and Lee, E. Y. (1999) BRCA2 is required for ionizing radiation-induced assembly of Rad51 complex in vivo. Cancer Res. 59, 3547-3551 (Pubitemid 29381849)
23. Long, X., Boluyt, M. O., Hipolito, M. L., Lundberg, M. S., Zheng, J. S., O'Neill, L., Cirielli, C., Lakatta, E. G., and Crow, M. T. (1997) p53 and the hypoxia-induced apoptosis of cultured neonatal rat cardiac myocytes. J. Clin. Investig. 99, 2635-2643 (Pubitemid 27259810)
24. Ludwig, T., Chapman, D. L., Papaioannou, V. E., and Efstratiadis, A. (1997) Targeted mutations of breast cancer susceptibility gene homologs in mice: lethal phenotypes of Brca1, Brca2, Brca1/Brca2, Brca1/p53, and Brca2/p53 nullizygous embryos. Genes Dev. 11, 1226-1241 (Pubitemid 27235356)
25. Basu, A., and Haldar, S. (1998) The relationship between BcI2, Bax and p53: consequences for cell cycle progression and cell death. Mol. Hum. Reprod 4, 1099-1109 (Pubitemid 28552792)
26. Hochhauser, E., Kivity, S., Offen, D., Maulik, N., Otani, H., Barhum, Y., Pannet, H., Shneyvays, V., Shainberg, A., Goldshtaub, V., Tobar, A., and Vidne, B. A. (2003) Bax ablation protects against myocardial ischemia-reperfusion injury in transgenic mice. Am. J. Physiol. Heart Circ. Physiol. 284, H2351-H2359 (Pubitemid 36622451)
27. Misao, J., Hayakawa, Y., Ohno, M., Kato, S., Fujiwara, T., and Fujiwara, H. (1996) Expression of bcl-2 protein, an inhibitor of apoptosis, and Bax, an accelerator of apoptosis, in ventricular myocytes of human hearts with myocardial infarction. Circulation 94, 1506-1512 (Pubitemid 26320251)
28. Hoeijmakers, J. H. (2001) Genome maintenance mechanisms for preventing cancer. Nature 411, 366-374
29. Di Padova, M., Bruno, T., De Nicola, F., Iezzi, S., D'Angelo, C., Gallo, R., Nicosia, D., Corbi, N., Biroccio, A., Floridi, A., Passananti, C., and Fanciulli, M. (2003) Che-1 arrests human colon carcinoma cell proliferation by displacing HDAC1 from the p21WAF1/CIP1 promoter. J. Biol. Chem. 278, 36496-36504 (Pubitemid 37139979)
30. Jiang, H., Reinhardt, H. C., Bartkova, J., Tommiska, J., Blomqvist, C., Nevanlinna, H., Bartek, J., Yaffe, M. B., and Hemann, M. T. (2009) The combined status ofATMand p53 link tumor development with therapeutic response. Genes Dev. 23, 1895-1909
31. Kurz, E. U., Douglas, P., and Lees-Miller, S. P. (2004) Doxorubicin activates ATM-dependent phosphorylation of multiple downstream targets in part through the generation of reactive oxygen species. J. Biol. Chem. 279, 53272-53281 (Pubitemid 40051831)
32. Welcsh, P. L., and King, M. C. (2001) BRCA1 and BRCA2 and the genetics of breast and ovarian cancer. Hum. Mol. Genet. 10, 705-713 (Pubitemid 32331579)
33. Davies, A. A., Masson, J. Y., McIlwraith, M. J., Stasiak, A. Z., Stasiak, A., Venkitaraman, A. R., and West, S. C. (2001) Role of BRCA2 in control of the RAD51 recombination and DNA repair protein. Mol. Cell 7, 273-282 (Pubitemid 32206495)
34. Yang, H., Jeffrey, P. D., Miller, J., Kinnucan, E., Sun, Y., Thoma, N. H., Zheng, N., Chen, P. L., Lee, W. H., and Pavletich, N. P. (2002) BRCA2 function in DNA binding and recombination from a BRCA2-DSS1-ss-DNA structure. Science 297, 1837-1848 (Pubitemid 35024337)
35. Botto, N., Rizza, A., Colombo, M. G., Mazzone, A. M., Manfredi, S., Masetti, S., Clerico, A., Biagini, A., and Andreassi, M. G. (2001) Evidence forDNAdamage in patients with coronary artery disease. Mutat. Res. 493, 23-30 (Pubitemid 32539427)
36. Tsutsui, H., Ide, T., Shiomi, T., Kang, D., Hayashidani, S., Suematsu, N., Wen, J., Utsumi, H., Hamasaki, N., and Takeshita, A. (2001) 8-Oxo-dGTPase, which prevents oxidative stress-induced DNA damage, increases in the mitochondria from failing hearts. Circulation 104, 2883-2885 (Pubitemid 33139097)
37. DeGeorge, B. R., Jr., Gao, E., Boucher, M., Vinge, L. E., Martini, J. S., Raake, P. W., Chuprun, J. K., Harris, D. M., Kim, G. W., Soltys, S., Eckhart, A. D., and Koch, W. J. (2008) Targeted inhibition of cardiomyocyte Gi signaling enhances susceptibility to apoptotic cell death in response to ischemic stress. Circulation 117, 1378-1387 (Pubitemid 351501491)
38. 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
39. Bordeleau, L., Lipscombe, L., Lubinski, J., Ghadirian, P., Foulkes, W. D., Neuhausen, S., Ainsworth, P., Pollak, M., Sun, P., and Narod, S. A. (2011) Diabetes and breast cancer among women with BRCA1 and BRCA2 mutations. Cancer 117, 1812-1818
40. Mai, P. L., Chatterjee, N., Hartge, P., Tucker, M., Brody, L., Struewing, J. P., and Wacholder, S. (2009) Potential excess mortality in BRCA1/2 mutation carriers beyond breast, ovarian, prostate, and pancreatic cancers, and melanoma. PLoS One 4, e4812
41. Tavtigian, S. V., Simard, J., Rommens, J., Couch, F., Shattuck-Eidens, D., Neuhausen, S., Merajver, S., Thorlacius, S., Offit, K., Stoppa-Lyonnet, D., Belanger, C., Bell, R., Berry, S., Bogden, R., Chen, Q., Davis, T., Dumont, M., Frye, C., Hattier, T., Jammulapati, S., Janecki, T., Jiang, P., Kehrer, R., Leblanc, J. F., Mitchell, J. T., McArthur-Morrison, J., Nguyen, K., Peng, Y., Samson, C., Schroeder, M., Snyder, S. C., Steele, L., Stringfellow, M., Stroup, C., Swedlund, B., Swense, J., Teng, D., Thomas, A., Tran, T., Tranchant, M., Weaver-Feldhaus, J., Wong, A. K., Shizuya, H., Eyfjord, J. E., Cannon-Albright, L., Tranchant, M., Labrie, F., Skolnick, M. H., Weber, B., Kamb, A., and Goldgar, D. E. (1996) The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds. Nat. Genet. 12, 333-337 (Pubitemid 26080098)
42. McAllister, K. A., Haugen-Strano, A., Hagevik, S., Brownlee, H. A., Collins, N. K., Futreal, P. A., Bennett, L. M., and Wiseman, R. W. (1997) Characterization of the rat and mouse homologues of the BRCA2 breast cancer susceptibility gene. Cancer Res. 57, 3121-3125 (Pubitemid 27351722)
43. Lu, H., Guo, X., Meng, X., Liu, J., Allen, C., Wray, J., Nickoloff, J. A., and Shen, Z. (2005) The BRCA2-interacting protein BCCIP functions in RAD51 and BRCA2 focus formation and homologous recombinational repair. Mol. Cell. Biol. 25, 1949-1957 (Pubitemid 40280157)
44. Saleh-Gohari, N., and Helleday, T. (2004) Conservative homologous recombination preferentially repairs DNA double-strand breaks in the S phase of the cell cycle in human cells. Nucleic Acids Res. 32, 3683-3688 (Pubitemid 39157716)
45. Holloman, W. K. (2011) Unraveling the mechanism of BRCA2 in homologous recombination. Nat. Struct. Mol. Biol. 18, 748-754
46. Lebrecht, D., and Walker, U. A. (2007) Role of mtDNA lesions in anthracycline cardiotoxicity. Cardiovasc. Toxicol. 7, 108-113 (Pubitemid 47339856)
47. L'Ecuyer, T., Sanjeev, S., Thomas, R., Novak, R., Das, L., Campbell, W., and Heide, R. V. (2006) DNA damage is an early event in doxorubicin-induced cardiac myocyte death. Am. J. Physiol. Heart Circ. Physiol. 291, H1273-H1280 (Pubitemid 44343672)
48. Bergmann, O., Bhardwaj, R. D., Bernard, S., Zdunek, S., Barnabé-Heider, F., Walsh, S., Zupicich, J., Alkass, K., Buchholz, B. A., Druid, H., Jovinge, S., and Frisén, J. (2009) Evidence for cardiomyocyte renewal in humans. Science 324, 98-102
49. Beltrami, A. P., Urbanek, K., Kajstura, J., Yan, S. M., Finato, N., Bussani, R., Nadal-Ginard, B., Silvestri, F., Leri, A., Beltrami, C. A., and Anversa, P. (2001) Evidence that human cardiac myocytes divide after myocardial infarction. N. Engl. J. Med. 344, 1750-1757 (Pubitemid 32497029)
50. Kondo, N., Takahashi, A., Mori, E., Noda, T., Zdzienicka, M. Z., Thompson, L. H., Helleday, T., Suzuki, M., Kinashi, Y., Masunaga, S., Ono, K., Hasegawa, M., and Ohnishi, T. (2011) FANCD1/BRCA2 plays predominant role in the repair of DNA damage induced by ACNU or TMZ. PLoS One 6, e19659
51. Shukla, P. C., Singh, K. K., Quan, A., Al-Omran, M., Teoh, H., Lovren, F., Cao, L., Rovira, I. I., Pan, Y., Brezden-Masley, C., Yanagawa, B., Gupta, A., Deng, C. X., Coles, J. G., Leong-Poi, H., Stanford, W. L., Parker, T. G., Schneider, M. D., Finkel, T., and Verma, S. (2011) BRCA1 is an essential regulator of heart function and survival following myocardial infarction. Nat. Commun. 2, 593
52. Teoh, H., Quan, A., Creighton, A. K., Bang, K. W., Singh, K. K., Shukla, P. C., Gupta, N., Pan, Y., Lovren, F., Leong-Poi, H., Al-Omran, M., and Verma, S. (2012) BRCA1 gene therapy reduces systemic inflammatory response and multiple organ failure and improves survival in experimental sepsis. Gene Ther. 10 1038/gt.2011.214