Open Access

Aminosalicylic acid reduces ER stress and Schwann cell death induced by MPZ mutations

  • Authors:
    • Eun Hyuk Chang
    • Won Min Mo
    • Hyun Myung Doo
    • Ji‑Su Lee
    • Hwan Tae Park
    • Byung‑Ok Choi
    • Young Bin Hong
  • View Affiliations

  • Published online on: May 2, 2019     https://doi.org/10.3892/ijmm.2019.4178
  • Pages: 125-134
  • Copyright: © Chang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Mutations in myelin protein zero (MPZ) cause inherited peripheral neuropathies, including Charcot‑Marie‑Tooth disease (CMT) and Dejerine‑Sottas neuropathy. Mutant MPZ proteins have previously been reported to cause CMT via enhanced endoplasmic reticulum (ER) stress and Schwann cell (SC) death, although the pathological mechanisms have not yet been elucidated. In this study, we generated an in vitro model of rat SCs expressing mutant MPZ (MPZ V169fs or R98C) proteins and validated the increase in cell death and ER stress induced by the overexpression of the MPZ mutants. Using this model, we examined the efficacy of 3 different aminosalicylic acids (ASAs; 4‑ASA, sodium 4‑ASA and 5‑ASA) in alleviating pathological phenotypes. FACS analysis indicated that the number of apoptotic rat SCs, RT4 cells, induced by mutant MPZ overexpression was significantly reduced following treatment with each ASA. In particular, treatment with 4‑ASA reduced the levels of ER stress markers in RT4 cells induced by V169fs MPZ mutant overexpression and relieved the retention of V169fs mutant proteins in the ER. Additionally, the level of an apoptotic signal mediator (p‑JNK) was only decreased in the RT4 cells expressing R98C MPZ mutant protein following treatment with 4‑ASA. Although 4‑ASA is known as a free radical scavenger, treatment with 4‑ASA in the in vitro model did not moderate the level of reactive oxygen species, which was elevated by the expression of mutant MPZ proteins. On the whole, the findings of this study indicate that treatment with 4‑ASA reduced the ER stress and SC death caused by 2 different MPZ mutants and suggest that ASA may be a potential therapeutic agent for CMT.
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July-2019
Volume 44 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Chang EH, Mo WM, Doo HM, Lee JS, Park HT, Choi BO and Hong YB: Aminosalicylic acid reduces ER stress and Schwann cell death induced by MPZ mutations. Int J Mol Med 44: 125-134, 2019.
APA
Chang, E.H., Mo, W.M., Doo, H.M., Lee, J., Park, H.T., Choi, B., & Hong, Y.B. (2019). Aminosalicylic acid reduces ER stress and Schwann cell death induced by MPZ mutations. International Journal of Molecular Medicine, 44, 125-134. https://doi.org/10.3892/ijmm.2019.4178
MLA
Chang, E. H., Mo, W. M., Doo, H. M., Lee, J., Park, H. T., Choi, B., Hong, Y. B."Aminosalicylic acid reduces ER stress and Schwann cell death induced by MPZ mutations". International Journal of Molecular Medicine 44.1 (2019): 125-134.
Chicago
Chang, E. H., Mo, W. M., Doo, H. M., Lee, J., Park, H. T., Choi, B., Hong, Y. B."Aminosalicylic acid reduces ER stress and Schwann cell death induced by MPZ mutations". International Journal of Molecular Medicine 44, no. 1 (2019): 125-134. https://doi.org/10.3892/ijmm.2019.4178