Molecules and Cells

  • 제28권5호
  • /
  • Pages.495-499
  • /
  • 2009
  • /
  • 1016-8478(pISSN)
  • /
  • 0219-1032(eISSN)
한국분자세포생물학회 (Korean Society for Molecular and Cellular Biology)
권호 표지
DOI QR코드

DOI QR Code

Insulin-Like Growth Factor-I-Induced Androgen Receptor Activation Is Mediated by the PI3K/Akt Pathway in C2C12 Skeletal Muscle Cells

  • Lee, Won Jun (Department of Exercise Science, College of Health Sciences, Ewha Womans University)
  • 투고 : 2009.08.12
  • 심사 : 2009.09.07
  • 발행 : 2009.11.30
⟨ 이전 논문 다음 논문 ⟩

초록

Although insulin-like growth factor-I (IGF-I) and androgen receptor (AR) are well known effectors of skeletal muscle, the molecular mechanism by which signaling pathways integrating AR and IGF-I in skeletal muscle cells has not been previously examined. In this study, the role of PI3K/Akt on IGF-I-induced gene expression and activation of AR in skeletal muscle cells was investigated. C2C12 cells were treated with IGF-I in the absence or presence of inhibitors of PI3K/Akt pathway (LY294002 and Wortmannin). Inhibition of the PI3K/Akt pathway with LY294002 or Wortmannin led to a significant decrease in IGF-I-induced AR phosphorylation and total AR protein expression. Furthermore, IGF-I-induced AR mRNA and skeletal ${\alpha}-actin$ mRNA were blocked by LY294002 or Wortmannin. Confocal images showed that IGF-I-induced AR translocation from cytosol to nucleus was inhibited significantly in response to treatment with LY294002 or Wortmannin. The present results suggest that modulating effect of IGF-I on AR gene expression and activation in C2C12 mouse skeletal muscle cells is mediated at least in part by the PI3K/Akt pathway.

키워드

과제정보

연구 과제 주관 기관 : Korean Research Foundation

참고문헌

  1. Bodine, S.C., Stitt, T.N., Gonzalez, M., Kline, W.O., Stover, G.L., Bauerlein, R., Zlotchenko, E., Scrimgeour, A., Lawrence, J.C., Glass, D.J., et al. (2001). Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo. Nat. Cell Biol. 3, 1014-1019 https://doi.org/10.1038/ncb1101-1014
  2. Butler, A.A., Yakar, S., Gewolb, I.H., Karas, M., Okubo, Y., and LeRoith, D. (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
  3. Culig, Z., Hobisch, A., Cronauer, M.V., Radmayr, C., Trapman, J., Hittmair, A., Bartsch, G., and Klocker, H. (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
  4. DeVol, D.L., Rotwein, P., Sadow, J.L., Novakofski, J., and Bechtel, P.J. (1990). Activation of insulin-like growth factor gene expression during work-induced skeletal muscle growth. Am. J. Physiol. 259, E89-E95
  5. Franke, T.F., Kaplan, D.R., and Cantley, L.C. (1997). PI3K: Downstream AKTion blocks apoptosis. Cell 88, 435-437 https://doi.org/10.1016/S0092-8674(00)81883-8
  6. Frost, R.A., and Lang, C.H. (1999). Differential effects of insulin-like growth factor I (IGF-I) and IGF-binding protein-1 on protein metabolism in human skeletal muscle cells. Endocrinology 140, 3962-3970 https://doi.org/10.1210/en.140.9.3962
  7. Lee, D.K. (2002). Androgen receptor enhances myogenin expression and accelerates differentiation. Biochem. Biophys. Res. Commun. 294, 408-413 https://doi.org/10.1016/S0006-291X(02)00504-1
  8. Lee, W.J., Thompson, R.W., McClung, J.M., and Carson, J.A. (2003). Regulation of androgen receptor expression at the onset of functional overload in rat plantaris muscle. Am. J. Physiol. 285, R1076-R1085
  9. Lin, H.K., Yeh, S., Kang, H.Y., and Chang, C. (2001). Akt suppresses androgen-induced apoptosis by phosphorylating and inhibiting androgen receptor. Proc. Natl. Acad. Sci. USA 98, 7200-7205 https://doi.org/10.1073/pnas.121173298
  10. Lin, H.K., Wang, L., Hu, Y.C., Altuwaijri, S., and Chang, C. (2002). Phosphorylation-dependent ubiquitylation and degradation of androgen receptor by Akt require Mdm2 E3 ligase. EMBO J. 21, 4037-4048 https://doi.org/10.1093/emboj/cdf406
  11. Lin, H.K., Hu, Y.C., Yang, L., Altuwaijri, S., Chen, Y.T., Kang, H.Y., and Chang, C. (2003). Suppression versus induction of androgen receptor functions by the phosphatidylinositol 3-kinase/Akt pathway in prostate cancer LNCaP cells with different passage numbers. J. Biol. Chem. 278, 50902-50907 https://doi.org/10.1074/jbc.M300676200
  12. Lu, S., Liu, M., Epner, D.E., Tsai, S.Y., and Tsai, M.J. (1999). Androgen regulation of the cyclin-dependent kinase inhibitor p21 gene through an androgen response element in the proximal promoter. Mol. Endocrinol. 13, 376-384 https://doi.org/10.1210/me.13.3.376
  13. Meng, D., Shi, X., Jiang, B.H., and Fang, J. (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
  14. Musaro, A., McCullagh, K.J., Naya, F.J., Olson, E.N., and Rosenthal, N. (1999). IGF-I induces skeletal myocyte hypertrophy through calcineurin in association with GATA-2 and NF-ATc1. Nature 400, 581-585 https://doi.org/10.1038/23060
  15. Rommel, C., Bodine, S.C., Clarke, B.A., Rossman, R., Nunez, L., Stitt, T.N., and Glass, D.J. (2001). Mediation of IGF-I-induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3) K/Akt/GSK3 pathways. Nat. Cell Biol. 3, 1009-1013 https://doi.org/10.1038/ncb1101-1009
  16. Wen, Y., Hu, M.C., Makino, K., Spohn, B., Bartholomeusz, G., Yan, D.H., and Hung, M.C. (2000). HER-2/neu promotes androgenindependent survival and growth of prostate cancer cells through the Akt pathway. Cancer Res. 60, 6841-6845
  17. Wu, J.D., Haugk, K., Woodke, L., Nelson, P., Coleman, I., and Plymate, S.R. (2006). Interaction of IGF-signaling and the androgen receptor in prostate cancer progression. J. Cell. Biochem. 99, 392-401

피인용 문헌

  1. Insulin stimulation of Akt/PKB phosphorylation in the placenta of preeclampsia patients vol.129, pp.6, 2009, https://doi.org/10.1590/s1516-31802011000600004
  2. Regulation of the androgen receptor by post-translational modifications vol.215, pp.2, 2009, https://doi.org/10.1530/joe-12-0238
  3. Activated Integrin-Linked Kinase Negatively Regulates Muscle Cell Enhancement Factor 2C in C2C12 Cells vol.2015, pp.None, 2015, https://doi.org/10.1155/2015/748470
  4. Testosterone insulin-like effects: an in vitro study on the short-term metabolic effects of testosterone in human skeletal muscle cells vol.40, pp.10, 2009, https://doi.org/10.1007/s40618-017-0686-y
  5. Phosphorylated GSK-3β protects stress-induced apoptosis of myoblasts via the PI3K/Akt signaling pathway vol.22, pp.1, 2020, https://doi.org/10.3892/mmr.2020.11105
  6. Activation of IGF-1 pathway and suppression of atrophy related genes are involved in Epimedium extract (icariin) promoted C2C12 myotube hypertrophy vol.11, pp.1, 2009, https://doi.org/10.1038/s41598-021-89039-0
  7. Androgen receptor regulates the proliferation of myoblasts under appropriate or excessive stretch through IGF-1 receptor mediated p38 and ERK1/2 pathways vol.18, pp.1, 2009, https://doi.org/10.1186/s12986-021-00610-y