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The Establishment of Tumor Necrosis Factor Receptor-associated Protein1 (TRAP1) Transgenic Mice and Severe Fat Accumulation in the Liver of TRAP1 Mice during Liver Regeneration

  • Im, Chang-Nim (Department of Biochemistry and Molecular Biology, College of Medicine, Seoul National University) ;
  • Zheng, Ying (Department of Biochemistry and Molecular Biology, College of Medicine, Seoul National University) ;
  • Kim, Sun Hye (Department of Biochemistry and Molecular Biology, College of Medicine, Seoul National University) ;
  • Huang, Tai-Qin (Department of Biochemistry and Molecular Biology, College of Medicine, Seoul National University) ;
  • Cho, Du-Hyong (Department of Neurology, Konkuk University Medical Center, Konkuk University) ;
  • Seo, Jeong-Sun (Department of Biochemistry and Molecular Biology, College of Medicine, Seoul National University)
  • Received : 2013.11.22
  • Accepted : 2013.12.24
  • Published : 2013.12.31

Abstract

Introduction: Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a mitochondrial heat shock protein (HSP), which belongs to HSP90 family. It plays important roles in regulating mitochondrial integrity, protecting against oxidative stress, and inhibiting cell death. Recent studies suggest that TRAP1 is linked to mitochondria and its metabolism. In this study, we established TRAP1 transgenic mice and performed partial hepatectomy (PH) on wild-type (WT) and TRAP1 transgenic mice to investigate the function of TRAP1 during liver regeneration. Results and Discussion: We found that TRAP1 was highly expressed in liver as well as kidney. In addition, liver regeneration slightly decreased together with increased fatty liver and inflammation at 72 hr after PH in TRAP1 transgenic mice compared with WT control group mice. Concomitantly, we observed decreased levels of p38 protein in TRAP1 transgenic mice compared with WT control group mice. These results suggest that TRAP1 plays a critical role in liver energy balance by regulating lipid accumulation during liver regeneration. Conclusions and Prospects: To our knowledge, we reported, for the first time, that liver regeneration slightly reduced together with increased fat accumulations after PH in TRAP1 transgenic mice compared with WT control group mice. Concomitantly, we observed decreased levels of p38 protein in TRAP1 transgenic mice compared with WT control group mice. Overexpression of TRAP1 might affect liver regeneration via disturbing mitochondrial function leading to fatty liver in vivo.

References

  1. Felts, S. J., Owen, B. A., Nguyen, P., Trepel, J., Donner, D. B., and Toft, D. O. (2000). The hsp90-related protein TRAP1 is a mitochondrial protein with distinct functional properties. The Journal of Biological Chemistry 275, 3305-3312. https://doi.org/10.1074/jbc.275.5.3305
  2. Kang, B. H. (2012). TRAP1 regulation of mitochondrial life or death decision in cancer cells and mitochondria-targeted TRAP1 inhibitors. BMB Reports 45, 1-6. https://doi.org/10.5483/BMBRep.2012.45.1.1
  3. Hua, G., Zhang, Q., and Fan, Z. (2007). Heat shock protein 75 (TRAP1) antagonizes reactive oxygen species generation and protects cells from granzyme M-mediated apoptosis. The Journal of Biological Chemistry 282, 20553-20560. https://doi.org/10.1074/jbc.M703196200
  4. Im, C. N., Lee, J. S., Zheng, Y., and Seo, J. S. (2007). Iron chelation study in a normal human hepatocyte cell line suggests that tumor necrosis factor receptor-associated protein 1 (TRAP1) regulates production of reactive oxygen species. Journal of Cellular Biochemistry 100, 474-486. https://doi.org/10.1002/jcb.21064
  5. Masuda, Y., Shima, G., Aiuchi, T., Horie, M., Hori, K., Nakajo, S., Kajimoto, S., Shibayama-Imazu, T., and Nakaya, K. (2004). Involvement of tumor necrosis factor receptor-associated protein 1 (TRAP1) in apoptosis induced by beta-hydroxyisovalerylshikonin. The Journal of Biological Chemistry 279, 42503-42515. https://doi.org/10.1074/jbc.M404256200
  6. Pridgeon, J. W., Olzmann, J. A., Chin, L. S., and Li, L. (2007). PINK1 protects against oxidative stress by phosphorylating mitochondrial chaperone TRAP1. PLoS Biology 5, e172. https://doi.org/10.1371/journal.pbio.0050172
  7. Takamura, H., Koyama, Y., Matsuzaki, S., Yamada, K., Hattori, T., Miyata, S., Takemoto, K., Tohyama, M., and Katayama, T. (2012). TRAP1 controls mitochondrial fusion/fission balance through Drp1 and Mff expression. PloS one 7, e51912. https://doi.org/10.1371/journal.pone.0051912
  8. Zhang, Y., Jiang, D. S., Yan, L., Cheng, K. J., Bian, Z. Y., and Lin, G. S. (2011). HSP75 protects against cardiac hypertrophy and fibrosis. Journal of Cellular Biochemistry 112, 1787-1794. https://doi.org/10.1002/jcb.23091
  9. Yoshida, S., Tsutsumi, S., Muhlebach, G., Sourbier, C., Lee, M. J., Lee, S., Vartholomaiou, E., Tatokoro, M., Beebe, K., Miyajima, N., et al. (2013). Molecular chaperone TRAP1 regulates a metabolic switch between mitochondrial respiration and aerobic glycolysis. Proceedings of the National Academy of Sciences of the United States of America 110, E1604-1612.
  10. Grattagliano, I., Russmann, S., Diogo, C., Bonfrate, L., Oliveira, P. J., Wang, D. Q., and Portincasa, P. (2011). Mitochondria in chronic liver disease. Current Drug Targets 12, 879-893. https://doi.org/10.2174/138945011795528877
  11. Taub, R. (2004). Liver regeneration: from myth to mechanism. Nature reviews Molecular Cell Biology 5, 836-847. https://doi.org/10.1038/nrm1489
  12. Fausto, N., Campbell, J. S., and Riehle, K. J. (2006). Liver regeneration. Hepatology 43, S45-53. https://doi.org/10.1002/hep.20969
  13. Kang, B. H., Plescia, J., Dohi, T., Rosa, J., Doxsey, S. J., and Altieri, D. C. (2007). Regulation of tumor cell mitochondrial homeostasis by an organelle- specific Hsp90 chaperone network. Cell 131, 257-270. https://doi.org/10.1016/j.cell.2007.08.028
  14. Song, H. Y., Dunbar, J. D., Zhang, Y. X., Guo, D., and Donner, D. B. (1995). Identification of a protein with homology to hsp90 that binds the type 1 tumor necrosis factor receptor. The Journal of Biological Chemistry 270, 3574-3581. https://doi.org/10.1074/jbc.270.8.3574
  15. Im, C. N., and Seo, J. S. (2013). Overexpression of tumor necrosis factor receptor-associated protein 1 (TRAP1), leads to mitochondrial aberrations in mouse fibroblast NIH/3T3 cells. BMB Reports.
  16. Grisham, J. W. (1962). A morphologic study of deoxyribonucleic acid synthesis and cell proliferation in regenerating rat liver; autoradiography with thymidine-H3. Cancer Research 22, 842-849.
  17. Campbell, J. S., Argast, G. M., Yuen, S. Y., Hayes, B., and Fausto, N. (2011). Inactivation of p38 MAPK during liver regeneration. The International Journal of Biochemistry & Cell Biology 43, 180-188. https://doi.org/10.1016/j.biocel.2010.08.002
  18. Colak, D., Chishti, M. A., Al-Bakheet, A. B., Al-Qahtani, A., Shoukri, M. M., Goyns, M. H., Ozand, P. T., Quackenbush, J., Park, B. H., and Kaya, N. (2010). Integrative and comparative genomics analysis of early hepatocellular carcinoma differentiated from liver regeneration in young and old. Molecular Cancer 9, 146. https://doi.org/10.1186/1476-4598-9-146
  19. Rohlfing, A. K., Trescher, K., Hahnel, J., Muller, C., and Hildebrandt, J. P. (2013). Partial hepatectomy in rats results in immediate down-regulation of p27Kip1 in residual liver tissue by transcriptional and posttranslational processes. Frontiers in Physiology 4, 139.
  20. Yang, S., Leow, C. K., and Tan, T. M. (2006). Expression patterns of cytokine, growth factor and cell cycle-related genes after partial hepatectomy in rats with thioacetamide-induced cirrhosis. World Journal of Gastroenterology: WJG 12, 1063-1070. https://doi.org/10.3748/wjg.v12.i7.1070
  21. Seo, J. S., Park, Y. M., Kim, J. I., Shim, E. H., Kim, C. W., Jang, J. J., Kim, S. H., and Lee, W. H. (1996). T cell lymphoma in transgenic mice expressing the human Hsp70 gene. Biochemical and Biophysical Research Communications 218, 582-587. https://doi.org/10.1006/bbrc.1996.0103
  22. Higgins, G. M. P. J. T. (1931) Experimental pathology of the liver I. Archives of Pathology. pp. 186-202.

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