Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
권호 표지
DOI QR코드

DOI QR Code

Insulin-Like Growth Factor-I Induces Androgen Receptor Coactivator Expression in Skeletal Muscle Cells through the p38 MAPK and ERK1/2 Pathways

C2C12 세포에서 insulin-like growth factor-I이 p38 MAPK, ERK1/2 신호전달 경로를 통해 엔드로젠 수용체 coactivator 발현에 미치는 영향

  • Park, Chan-Ho (Department of Physical Education, Pusan National University) ;
  • Kim, Hye-Jin (Department of Exercise Science, College of Health Sciences, Ewha Womans University) ;
  • Kim, Tae-Un (Department of Physical Education, Pusan National University) ;
  • Lee, Won-Jun (Department of Exercise Science, College of Health Sciences, Ewha Womans University)
  • 박찬호 (부산대학교 체육교육학과) ;
  • 김혜진 (이화여자대학교 건강과학대학 체육과학과) ;
  • 김태운 (부산대학교 체육교육학과) ;
  • 이원준 (이화여자대학교 건강과학대학 체육과학과)
  • Received : 2010.10.15
  • Accepted : 2010.11.17
  • Published : 2011.02.28
Download PDF
⟨ Previous Next ⟩

Abstract

Although insulin-like growth factor-I (IGF-I) and androgen receptor (AR) coactivators are well known effectors of skeletal muscle, the molecular mechanism by which signaling pathways integrating AR coactivators and IGF-I in skeletal muscle cells has not been previously examined. In this study, the effects of IGF-I treatment on the gene expression of AR coactivators in the absence of AR ligands and the roles of the p38 MAPK and ERK1/2 signaling pathways in IGF-I-induced AR coactivators induction were examined. C2C12 cells were treated with 250 ng/ml of IGF-I in the presence or absence of specific inhibitors p38 MAPK (SB203580) or ERK1/2 (PD98059). Treatment of C2C12 cells with IGF-I resulted in increased in GRIP-1, SRC-1, and ARA70 protein expression. The levels of GRIP-1, SRC-1, and ARA70 mRNA were also significantly increased after 5min of IGF-I treatment. IGF-I-induced AR coactivator proteins were significantly blocked by pharmacological inhibitors of p38 MAPK and ERK1/2 pathways. However, there was no significant effect of those inhibitors on IGF-I-induced mRNA level of AR coactivators, suggesting that AR coactivators are post-transcriptionally regulated by IGF-I. Furthermore, the present results suggest that IGF-I stimulates the expression of AR coactivators by cooperative activation of the p38 MAPK and ERK1/2 pathways in C2C12 mouse skeletal muscle cells.

본 연구에서는 C2C12 근육 세포에서 IGF-I이 리간드 비의존적으로 엔드로젠 수용체 coactivator 유전자 발현에 미치는 영향에 대해 알아보았다. 그 결과 IGF-I 이 리간드 비의존적으로 엔드로젠 수용체의 coactivator인 GRIP-1, SRC-1, ARA70 유전자들의 단백질과 mRNA 발현을 증가시켰으며, p38 MAPK와 ERK1/2 신호전달 경로 억제제인 SB203580과 PD98059를 IGF-I과 함께 처리한 결과 IGF-I에 의한 엔드로젠 수용체 coactivator 유전자 발현의 증가를 감소시켰음을 알 수 있었다. 엔드로젠 수용체 coactivator가 엔드로젠 물질이 없이도 IGF-I에 의해 발현이 증가하였다는 사실은 운동에 의해 근육에서 분비가 증가하는 IGF-I이 리간드 비의존적으로 근육 세포에서 엔드로젠 수용체 활성화 안정에 기여하는 엔드로젠 수용체 coactivator를 활성화 시킬 수 있다는 사실을 증명 하였다는데 의의가 있다고 사료된다. 또한, IGF-I의 하부신호전달 경로로 잘 알려진 p38 MAPK와 ERK1/2 신호전달 경로를 차단하였을 때는 발현이 억제되었는데 이를 통해 IGF-I이 근육세포 내에서 p38 MAPK, ERK1/2 경로를 통해 엔드로젠 수용체 coactivator 발현에 중요한 역할을 한다는 사실을 확인할 수 있었다. 이러한 결과는 근육에서 중요한 기능을 담당하는 IGF-I이 엔드로젠 수용체 coactivator 유전자 발현을 조절하는 기능이 있으며 이러한 IGF-I에 의한 리간드 비의존적인 엔드로젠 수용체 coactivator 유전자 발현 조절에 있어 p38 MAPK와 ERK1/2는 필수적인 신호전달 경로임을 확인하였다는 데서 그 의의가 있다고 할 수 있겠다. 향후 다양한 성장인자들에 의한 coactivator 발현에 관한 연구를 비롯하여, corepressor의 발현 억제 기능 및 신호전달 경로에 관한 연구가 추가적으로 이루어져야 할 것이다.

Keywords

References

  1. Antonio, J., J. D, Wilson, and F. W. George. 1999. Effects of castration and androgen treatment on androgen-receptor levels in rat skeletal muscles. J. Appl. Physiol. 87, 2016-2029.
  2. Anzick, S. L., J. Kononen, R. L. Walker, D. O. Azorsa, M. M. Tanner, X. Y. Guan, G. Sauter, O. P. Kallioniemi, J. M. Trent, and P. S. Meltzer. 1997. AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer. Science 277, 965-968. https://doi.org/10.1126/science.277.5328.965
  3. Bhasin, S., L. Woodhouse, and T. W. Storer. 2003. Androgen effects on body composition. Growth Horm. IGF Res. 13, S63-S71. https://doi.org/10.1016/S1096-6374(03)00058-3
  4. Butler, A. A., S. Yakar, I. H. Gewolb, M. Karas, Y. Okubo, and D. LeRoith. 1998. Insulin-like growth factor-I receptor signal transduction: at the interface between physiology and cell biology. Comp. Biochem. Mol. Biol. 121, 19-26. https://doi.org/10.1016/S0305-0491(98)10106-2
  5. Carlson, C. J., Z. Fan, S. E. Gordon, and F. W. Booth. 2001. Time course of the MAPK and PI3-kinase response within 24 h of skeletal muscle overload. J. Appl. Physiol. 91, 2079-2087.
  6. Coleman, M. E., F. DeMayo, K. C. Yin, H. M. Lee, R. Geske, C. Montgomery, and R. J. Schwartz. 1995. Myogenic vector expression of insulin-like growth factor I stimulates muscle cell differentiation and myofiber hypertrophy in transgenic mice. J. Biol. Chem. 270, 12109-12116. https://doi.org/10.1074/jbc.270.20.12109
  7. Culig, Z., A. Hobisch, M. V. Cronauer, C. Radmayr, J. Trapman, A. Hittmair, G. Bartsch, and H. Klocker. 1994. Androgen receptor activation in prostatic tumor cell lines by insulin-like growth factor-I, keratinocyte growth factor, and epidermal growth factor. Cancer Res. 54, 5474-5478.
  8. Florini, J. R., D. Z. Ewton, and S. A. Coolican. 1996. Growth hormone and the insulin-like growth factor system in myogenesis. Endocr. Rev. 16, 481-517.
  9. Francesca, W., C. Massimillino, G. Lucia, F. Andrea, B. Sergio, and M. Costanzo. 2008. Androgen receptor expression during C2C12 skeletal muscle cell line differentiation. Mol. Cell Endocrinol. 292, 11-19. https://doi.org/10.1016/j.mce.2008.05.018
  10. Francesco, O. Jr., T. Beatrice, G. Virginie, L. Serge, A. Christophe, S. Christian, and S. Charles. 2002. Potential action of IGF-I and EGF on androgen receptor nuclear transfer and transactivation in normal and cancer human prostate cell lines. Mol. Cell Endocrinol. 198, 105-114. https://doi.org/10.1016/S0303-7207(02)00374-X
  11. Galvin, C. D., O. Hardiman, and C. M. Nolan. 2003. IGF-I receptor mediates differentiation of primary cultures of mouse skeletal myoblasts. Mol. Cell Endocrinol. 200, 19-29. https://doi.org/10.1016/S0303-7207(02)00420-3
  12. Haddad, F and G. R. Adams. 2004. Inhibition of MAP/ERK kinase prevents IGF-I-induced hypertrophy in rat muscles. J. Appl. Physiol. 96, 203-210.
  13. Hao, S., M. S. Jason, W. Caiyun, M. P. Jonatha, M. H. Kevin, L. G. Alan, and E. G. David. 2009. Mitogen-activated protein kinase signaling is necessary for the maintenance of skeletal muscle mass. Am. J. Physiol. 296, C1040-1048. https://doi.org/10.1152/ajpcell.00475.2008
  14. Hill, M. and G. Goldspink. 2003. Expression and splicing of the insulin-like growth factor gene in rodent muscle is associated with muscle satellite (stem) cell activation following local tissue damage. J. Physiol. 549, 409-418. https://doi.org/10.1113/jphysiol.2002.035832
  15. Hu, Y. C., S. Yeh, S. D. Yeh, R. S. Erick, J. Huang, P. Li, C. L. Hsu, H. J. Ting, H. K. Lin, L. Wang, E. Kim, J. Ni, and C. Chang. 2004. Functional domain and motif analyses of androgen receptor coregulator ARA70 and its differential expression in prostate cancer. J. Biol. Chem. 279, 33438-33446. https://doi.org/10.1074/jbc.M401781200
  16. Jennifer, D. W., H. Kathy, W. Libby, N. Peter, C. Ilsa, and R. P. Stephen. 2006. Interaction of IGF Signaling and the androgen receptor in prostate cancer progression. J. Cell Biochem. 99, 392-401. https://doi.org/10.1002/jcb.20929
  17. Jennische, E. and H. A. Hansson. 1987. Regenerating skeletal muscle cells express insulin-like growth factor I. Acta Physiol. Scand. 130, 327-332. https://doi.org/10.1111/j.1748-1716.1987.tb08144.x
  18. Joanne, E. and M. S. John. 2005. The androgen receptor and signal-transduction pathways in hormone-refractory prostate cancer. Part 2: androgen receptor cofactors and bypass pathways. BJU Int. 95, 1327-1335. https://doi.org/10.1111/j.1464-410X.2005.05527.x
  19. Jones, J. I. and D. R. Clemmons. 1995. Insulin-like growth factors and their binding proteins: biological action. Endocr. Rev. 16, 3-34.
  20. Keren, A., Y. Tamir, and E. Bengal. 2006. The p38 MAPK signaling pathway: A major regulator of skeletal muscle development. Mol. Cell Endocrinol. 252, 224-230. https://doi.org/10.1016/j.mce.2006.03.017
  21. Kim, H. J. and W. J. Lee. 2009. Insulin-like growth factor-I induces androgen receptor activation in differentiating C2C12 skeletal muscle cells. Mol. Cells 28, 189-194. https://doi.org/10.1007/s10059-009-0118-8
  22. Lewis, M. I., G. D. Horritz, D. R. Clemmons, and M. Fournier. 2002. Role of IGF-I and IGF-binding proteins within diaphragm muscle in modulating the effects of nandrolone. Am. J. Physiol. 282, E483-490.
  23. Mangelsdorf, D. J., C. Thummel, M. Beato, P. Herrlich, G. Schutz, K. Umesono, B. Blumberg, P. Kastner, M. Mark, P. Chambon, and R. M. Evans. 1995. The nuclear receptor superfamily: the second decade. Cell 83, 835-839. https://doi.org/10.1016/0092-8674(95)90199-X
  24. McKenna, N. J., R. B. Lanz, and B. W. O'Mally. 1999. Nuclear receptor coregulators; cellular and molecular biology. Endocr. Rev. 20, 321-344. https://doi.org/10.1210/er.20.3.321
  25. McLellan, A. S., T. Kealey, and K. Langlands. 2006. An E box in the exon 1 promoter regulates insulin-like growth factor-I expression in differentiating muscle cells. Am. J. Physiol. 291, C300-C307. https://doi.org/10.1152/ajpcell.00345.2005
  26. Meng, D., X. Shi, B. H. Jiang, and J. Fang. 2007. Insulin-like growth factor-I (IGF-I) induces epidermal growth factor receptor transactivation and cell proliferation through reactive oxygen species. Free Radic. Biol. Med. 42, 1651-1660. https://doi.org/10.1016/j.freeradbiomed.2007.01.037
  27. Park, P. and P. Cohen. 2005. Insulin-like growth factor I (IGF-I) measurements in growth hormone (GH) therapy of idiopathic short stature (ISS). Growth Horm. IGF Res. 15, S13-20. https://doi.org/10.1016/j.ghir.2005.06.011
  28. Powell, S. M., V. Christiaens, D. Voulgaraki, J. Waxman, F. Claessens, and C. L. Bevan. 2004. Mechanisms of androgen receptor signalling via steroid receptor coactivator- 1 in prostate. Endocr. Relat. Cancer 11, 117-130. https://doi.org/10.1677/erc.0.0110117
  29. Rahman, M. M., H. Miyamoto, H. Takatera, S. Yeh, S.Altuwaijri, and C. Chang. 2003. Reducing the agonist activity of anti-androgens by a dominant-negative androgen receptor coregulator ARA70 in prostate cancer cells. J. Biol. Chem. 278, 19619-19626. https://doi.org/10.1074/jbc.M210941200
  30. Roy, A. K., R. K. Tyagi, C. S. Song, Y. Lavrovsky, S. C. Ahn, T. S. Oh, and B. Chatterjee. 2001. Androgen receptor: structural domains and functional dynamics after ligand-receptor interaction. Ann. NY. Acad. Sci. 949, 44-57.
  31. Siriett, V., G. Nicholas, C. Berry, T. Watson, A. Hennebry, M. Thomas, N. Ling, M. Sharma, and R. Kambadur. 2006. Myostatin negative regulates the expression of the steroid receptor co-factor ARA70. J. Cell Physiol. 206, 255-263. https://doi.org/10.1002/jcp.20456
  32. Suzuki, H., T. Ueda, T. Ichikawa, and H. Ito. 2003. Androgen receptor involvement in the progression of prostate cancer. Endocr. Relat. Cancer 10, 209-216. https://doi.org/10.1677/erc.0.0100209
  33. Takeshita, A., G. R. Cardona, N. Koibuchi, C. S. Suen, and W. W. Chin. 1997. TRAM-1, A novel 160-kDa thyroid hormone receptor activator molecule, exhibits distinct properties from steroid receptor coactivator-1. J. Biol. Chem. 272, 27629-27634. https://doi.org/10.1074/jbc.272.44.27629
  34. Touno, M., M. Senda, K. Nakago, Y. Yokoyama, and H. Inoue. 1996. Muscle fiber changes of the vastus medialis in rheumatoid patients. Acta. .Medica. Okayama. 50, 157-164.
  35. Ueda, T., D. T. Max, N. Bruchovsky, and M. D. Sadar. 2002. Ligand-independent activation of the androgen receptor by interlukin-6 and the role of steroid receptor coactivator- 1 in prostate cancer cells. J. Biol. Chem. 277, 38087-38094. https://doi.org/10.1074/jbc.M203313200
  36. Wu, Z., P. J. Woodring, K. S. Bhakta, K. Tamura, F. Wen, J. R. Feramisco, M. Karin, J. Y. Wang, and R. L. Puri. 2000. p38 and extra cellular signal regulated kinases regulate the myogenic program at multiple steps. Mol. Cell Endocrinol. 20, 3951-3964.
  37. Xu, L., C. K. Glass, and M. G. Rosenfeld. 1999. Coactivator and corepressor complexes in nuclear receptor function. Curr. Opin. Gent. Dev. 9, 140-147. https://doi.org/10.1016/S0959-437X(99)80021-5
  38. Yeh, S. and C. Chang. 1996. Cloning and characterization of a specific coactivator, ARA70, for the androgen receptor in human prostate cells. Proc. Natl. Acad. Sci. USA. 93, 5517-5521. https://doi.org/10.1073/pnas.93.11.5517
  39. Zester, A., E. Gredinger, and E. Bengal. 1999. p38 mitogen- activated protein kinase pathway promotes skeletal muscle differentiation. Participation of the Mef2c transcription factor. J. Biol. Chem. 274, 5193-5200. https://doi.org/10.1074/jbc.274.8.5193