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Nitric oxide inhibits ghrelin-induced cell proliferation and ERK1/2 activation in GH3 cells

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Abstract

Ghrelin stimulates growth hormone release and cell proliferation, which strongly supports a significant role for this peptide in the control of growth hormone-releasing adenomas function and growth. Nitric oxide can influence the stimulatory effects of ghrelin on growth hormone secretion in growth hormone-releasing adenomas. However, the effect of nitric oxide (NO) on ghrelin-induced cell proliferation and the mechanism of this effect in the adenoma were not clarified. In this study, we observed that ghrelin, at a concentration of 10−9 to 10−6 M, significantly increased BrdU incorporation into rat GH3 cells. A NO donor, S-nitroso-N-acetylpenicillamine (SNAP), blunted basal, and ghrelin-induced cell proliferation. A blocker of NO synthase, Nw-nitro-l-arginine methyl ester hydrochloride (NAME), had no influence on these actions. The activation of extracellular signal-regulated kinase (ERK) 1/2 was examined by western blotting. The results showed that SNAP reduced ghrelin-stimulated ERK1/2 activation but NAME had no influence on this activation. Together, this study indicates that NO inhibited ghrelin-induced cell proliferation by blocking ERK1/2 activation in GH3 cells.

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References

  1. M. Kojima, H. Hosoda, Y. Date, M. Nakazato, H. Matsuo, K. Kangawa, Nature 402(6762), 656–660 (1999)

    Article  CAS  PubMed  Google Scholar 

  2. A.J. van der Lely, M. Tschop, M.L. Heiman, E. Ghigo, Endocr. Rev. 25(3), 426–457 (2004)

    Article  PubMed  Google Scholar 

  3. A.P. Davenport, T.I. Bonner, S.M. Foord, A.J. Harmar, R.R. Neubig, J.P. Pin, M. Spedding, M. Kojima, K. Kangawa, Pharmacol. Rev. 57(4), 541–546 (2005)

    Article  CAS  PubMed  Google Scholar 

  4. A.D. Howard, S.D. Feighner, D.F. Cully, J.P. Arena, P.A. Liberator, C.I. Rosenblum, M. Hamelin, D.L. Hreniuk, O.C. Palyha, J. Anderson, P.S. Paress, C. Diaz, M. Chou, K.K. Liu, K.K. McKee, S.S. Pong, L.Y. Chaung, A. Elbrecht, M. Dashkevicz, R. Heavens, M. Rigby, D.J. Sirinathsinghji, D.C. Dean, D.G. Melillo, A.A. Patchett, R. Nargund, P.R. Griffin, J.A. DeMartino, S.K. Gupta, J.M. Schaeffer, R.G. Smith, L.H. Van der Ploeg, Science 273(5277), 974–977 (1996)

    Article  CAS  PubMed  Google Scholar 

  5. A.M. Nanzer, S. Kalaf, A.M. Mozid, R.C. Fowkes, M.V. Patel, J.M. Burrin, A.B. Grossman, M. Korbonits, Eur. J. Endocrinol. 151(2), 233–240 (2004)

    Article  CAS  PubMed  Google Scholar 

  6. A. Secondo, R. Sirabella, L. Formisano, A. D’ Alessio, P. Castaldo, S. Amoroso, P. Ingleton, G. Di Renzo, L. Annunziato, J. Neurochem. 84(6), 1367–1377 (2003)

    Article  CAS  PubMed  Google Scholar 

  7. M. Murata, Y. Okimura, K. Iida, M. Matsumoto, H. Sowa, H. Kaji, M. Kojima, K. Kangawa, K. Chihara, J. Biol. Chem. 277(7), 5667–5674 (2002)

    Article  CAS  PubMed  Google Scholar 

  8. D.S. Bredt, P.M. Hwang, S.H. Snyder, Nature 347(6295), 768–770 (1990)

    Article  CAS  PubMed  Google Scholar 

  9. C.G. Chamberlain, K.J. Mansfield, A. Cerra, Mol. Vis. 14, 983–991 (2008)

    CAS  PubMed  Google Scholar 

  10. B.H. Duvilanski, C. Zambruno, A. Seilicovich, D. Pisera, M. Lasaga, M.C. Diaz, N. Belova, V. Rettori, S.M. McCann, Proc. Natl Acad. Sci. USA 92(1), 170–174 (1995)

    Article  CAS  PubMed  Google Scholar 

  11. R. Volpi, P. Chiodera, G. Caffarri, P.P. Vescovi, L. Capretti, C. Gatti, V. Coiro, Neuropeptides 30(6), 528–532 (1996)

    Article  CAS  PubMed  Google Scholar 

  12. F. Rodríguez-Pacheco, R.M. Luque, M. Tena-Sempere, M.M. Malagón, J.P. Castaño, J. Neuroendocrinol. 20(3), 406–412 (2008)

    Article  PubMed  Google Scholar 

  13. H.P. Chen, L. Zhang, B.H. Xu, L.M. Kang, S.L. Yang, H.H. Zeng, X.Y. Shi, Tissue Cell 41(2), 133–140 (2009)

    Article  CAS  PubMed  Google Scholar 

  14. T. Rubinek, H. Rubinfeld, M. Hadani, G. Barkai, I. Shimon, Endocrine 28(2), 209–216 (2005)

    Article  CAS  PubMed  Google Scholar 

  15. A. Secondo, A. Pannaccione, M. Cataldi, R. Sirabella, L. Formisano, G. Di Renzo, L. Annunziato, Am. J. Physiol. Cell Physiol. 290(1), 233–243 (2006)

    Article  Google Scholar 

  16. M. Candolfi, G. Jaita, V. Zaldivar, S. Zarate, D. Pisera, A. Seilicovich, Neuroendocrinology 80(2), 83–91 (2004)

    Article  CAS  PubMed  Google Scholar 

  17. M. Volante, E. Allia, P. Gugliotta, A. Funaro, F. Broglio, R. Deghenghi, G. Muccioli, E. Ghigo, M. Papptti, J. Clin. Endocrinol. Metab. 87(3), 1300–1308 (2002)

    Article  CAS  PubMed  Google Scholar 

  18. M. Tsumori, Y. Murakami, K. Koshimura, Y. Kato, Endocr. J. 46(6), 779–785 (1999)

    Article  CAS  PubMed  Google Scholar 

  19. M. Tena-Sempere, L. Pinilla, D. Gonzalez, E. Aguilar, Neuroendocrinology 64(2), 146–152 (1996)

    Article  CAS  PubMed  Google Scholar 

  20. C.M. Cuttica, M. Giusti, L. Bocca, P. Sessarego, D. De Martini, S. Valenti, R. Spaziante, G. Giordano, Neuroendocrinology 66(6), 426–431 (1997)

    Article  CAS  PubMed  Google Scholar 

  21. D.H. Wang, Y.S. Hu, J.J. Du, Y.Y. Hu, W.D. Zhong, W.J. Qin, Endocrine 35(1), 112–117 (2009)

    Article  CAS  PubMed  Google Scholar 

  22. M.S. Kim, C.Y. Yoon, P.G. Jang, Y.J. Park, C.S. Shin, H.S. Park, J.W. Ryu, Y.K. Pak, J.Y. Park, K.U. Lee, S.Y. Kim, H.K. Lee, Y.B. Kim, K.S. Park, Mol. Endocrinol. 18(9), 2291–2301 (2004)

    Article  CAS  PubMed  Google Scholar 

  23. J. S. Gutkind, Sci. STKE. 2000(40), re1 (2000)

  24. H. Maekawa, K. Iwabuchi, I. Nagaoka, H. Watanabe, T. Kamano, M. Tsurumaru, Inflamm. Res. 49(10), 541–547 (2000)

    Article  CAS  PubMed  Google Scholar 

  25. G.H. Xue, J.W. Zhang, L. Zhang, H. Zhang, B.G. Zhang, Zhonghua Wai Ke Za Zhi 42(22), 1349–1352 (2004)

    PubMed  Google Scholar 

  26. D. Maulik, Q.M. Ashraf, O.P. Mishra, M. Delivoria-Papadopoulos, Neurosci. Lett. 439(1), 94–99 (2008)

    Article  CAS  PubMed  Google Scholar 

  27. I. Valverde, A. Penalva, E. Ghigo, F.F. Casanueva, C. Dieguez, Neuroendocrinology 74(4), 213–219 (2001)

    Article  CAS  PubMed  Google Scholar 

  28. C.N. Hall, J. Garthwaite, Nitric Oxide 21(2), 92–103 (2009)

    Article  CAS  PubMed  Google Scholar 

  29. D.D. Thomas, L.A. Ridnour, J.S. Isenberg, W. Flores-Santana, C.H. Switzer, S. Donzelli, P. Hussain, C. Vecoli, N. Paolocci, S. Ambs, C.A. Colton, C.C. Harris, D.D. Roberts, D.A. Wink, Biol. Med. 45(1), 18–31 (2008)

    CAS  Google Scholar 

  30. K.S. Madhusoodanan, F. Murad, Neurochem. Res. 32(4–5), 681–694 (2007)

    Article  CAS  PubMed  Google Scholar 

  31. T.S. Kostic, S.A. Andric, S.S. Stojilkovic, Mol. Endocrinol. 15(6), 1010–1022 (2001)

    Article  CAS  PubMed  Google Scholar 

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Acknowledgment

The authors acknowledge the support from the National Natural Science Foundation of China, Project No. 30672161.

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Authors and Affiliations

  1. Department of Neurosurgery, The First College of Clinical Medical Science, China Three Gorges University, Yichang Center People’s Hospital, Yi-Ling-Da-Dao, 183, Yichang, 443003, Hubei, People’s Republic of China

    Chunlei Tian, Lei Wang, Yuanguo Deng, Yuanxun Dong, Xiaodan Wang & Xiongwei Wang

  2. Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jie-Fang-Da-Dao, 1095, Wuhan, 430030, People’s Republic of China

    Fei Ye, Tongjiang Xu & Ting Lei

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  1. Chunlei Tian
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  2. Fei Ye
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Correspondence to Xiongwei Wang.

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Chunlei Tian and Fei Ye contributed equally to this work.

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Tian, C., Ye, F., Wang, L. et al. Nitric oxide inhibits ghrelin-induced cell proliferation and ERK1/2 activation in GH3 cells. Endocr 38, 412–416 (2010). https://doi.org/10.1007/s12020-010-9402-9

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  • DOI: https://doi.org/10.1007/s12020-010-9402-9

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