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Effects of ERK1/2 S-nitrosylation on ERK1/2 phosphorylation and cell survival in glioma cells

  • Authors:
    • Lei Jin
    • Yujia Cao
    • Tong Zhang
    • Peng Wang
    • Daofei Ji
    • Xuejiao Liu
    • Hengliang Shi
    • Lei Hua
    • Rutong Yu
    • Shangfeng Gao
  • View Affiliations / Copyright

    Affiliations: Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China, Department of Neurosurgery, People's Hospital of Gaoxin District, Suzhou, Jiangsu 215011, P.R. China, Department of Neurosurgery, Brain Hospital, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China
    Copyright: © Jin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1339-1348
    |
    Published online on: December 20, 2017
       https://doi.org/10.3892/ijmm.2017.3334
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Abstract

Aberrant activation of extracellular signal‑regulated kinase 1/2 (ERK1/2) by phosphorylation modification can trigger tumor cell development in glioma. S‑nitrosylation, which refers to the covalent addition of a nitric oxide (NO) group to a cysteine (Cys) thiol, is an important post‑translational modification that occurs on numerous cancer‑associated proteins. Protein S‑nitrosylation can increase or decrease protein activity and stability, and subsequent signal transduction and cellular processes. However, the association between ERK1/2 S‑nitrosylation and ERK1/2 phosphorylation, and the effects of ERK1 S‑nitrosylation on glioma cell survival are currently unknown. U251 glioma cells were treated with NO donors sodium nitroprusside (SNP) or S‑nitrosoglutathione (GSNO). CCK8 assay was used to assess the cell viability. NO levels in the medium were detected by Griess assay. Western blot analysis and biotin switch assay were employed to detect the ERK1/2 phosphorylation and S-nitrosylation. ERK1 wild-type and mutant plasmids were constructed, and used to transfect the U251 cells. Caspase-3 western blot analysis and flow cytometry were employed to assess cell apoptosis. The present study demonstrated that treatment with the NO donors SNP or GSNO led to an increase in ERK1/2 S‑nitrosylation, and a reduction in ERK1/2 phosphorylation, which was accompanied by growth inhibition of U251 glioma cells. Mutational analysis demonstrated that Cys183 was vital for S‑nitrosylation of ERK1, and that preventing ERK1 S‑nitrosylation by replacing Cys183 with alanine partially reversed GSNO‑induced cell apoptosis, and reductions in cell viability and ERK1/2 phosphorylation. In addition, increased ERK1/2 phosphorylation was associated with decreased ERK1/2 S‑nitrosylation in human glioma tissues. These findings identified the relationship between ERK1/2 S‑nitrosylation and phosphorylation in vitro and in vivo, and revealed a novel mechanism of ERK1/2 underlying tumor cell development and apoptotic resistance of glioma.
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Copy and paste a formatted citation
Spandidos Publications style
Jin L, Cao Y, Zhang T, Wang P, Ji D, Liu X, Shi H, Hua L, Yu R, Gao S, Gao S, et al: Effects of ERK1/2 S-nitrosylation on ERK1/2 phosphorylation and cell survival in glioma cells. Int J Mol Med 41: 1339-1348, 2018.
APA
Jin, L., Cao, Y., Zhang, T., Wang, P., Ji, D., Liu, X. ... Gao, S. (2018). Effects of ERK1/2 S-nitrosylation on ERK1/2 phosphorylation and cell survival in glioma cells. International Journal of Molecular Medicine, 41, 1339-1348. https://doi.org/10.3892/ijmm.2017.3334
MLA
Jin, L., Cao, Y., Zhang, T., Wang, P., Ji, D., Liu, X., Shi, H., Hua, L., Yu, R., Gao, S."Effects of ERK1/2 S-nitrosylation on ERK1/2 phosphorylation and cell survival in glioma cells". International Journal of Molecular Medicine 41.3 (2018): 1339-1348.
Chicago
Jin, L., Cao, Y., Zhang, T., Wang, P., Ji, D., Liu, X., Shi, H., Hua, L., Yu, R., Gao, S."Effects of ERK1/2 S-nitrosylation on ERK1/2 phosphorylation and cell survival in glioma cells". International Journal of Molecular Medicine 41, no. 3 (2018): 1339-1348. https://doi.org/10.3892/ijmm.2017.3334
Copy and paste a formatted citation
x
Spandidos Publications style
Jin L, Cao Y, Zhang T, Wang P, Ji D, Liu X, Shi H, Hua L, Yu R, Gao S, Gao S, et al: Effects of ERK1/2 S-nitrosylation on ERK1/2 phosphorylation and cell survival in glioma cells. Int J Mol Med 41: 1339-1348, 2018.
APA
Jin, L., Cao, Y., Zhang, T., Wang, P., Ji, D., Liu, X. ... Gao, S. (2018). Effects of ERK1/2 S-nitrosylation on ERK1/2 phosphorylation and cell survival in glioma cells. International Journal of Molecular Medicine, 41, 1339-1348. https://doi.org/10.3892/ijmm.2017.3334
MLA
Jin, L., Cao, Y., Zhang, T., Wang, P., Ji, D., Liu, X., Shi, H., Hua, L., Yu, R., Gao, S."Effects of ERK1/2 S-nitrosylation on ERK1/2 phosphorylation and cell survival in glioma cells". International Journal of Molecular Medicine 41.3 (2018): 1339-1348.
Chicago
Jin, L., Cao, Y., Zhang, T., Wang, P., Ji, D., Liu, X., Shi, H., Hua, L., Yu, R., Gao, S."Effects of ERK1/2 S-nitrosylation on ERK1/2 phosphorylation and cell survival in glioma cells". International Journal of Molecular Medicine 41, no. 3 (2018): 1339-1348. https://doi.org/10.3892/ijmm.2017.3334
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