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Valproic Acid Attenuated PTZ-induced Oxidative Stress, Inflammation, and Apoptosis in the SH-SY5Y Cells via Modulating the TRPM2 Channel

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Abstract

Valproic acid (VPA) is one of the most widely used antiepileptic drugs. The protective role of VPA and the role of the TRPM2 channel in this mechanism in developing neuronal damage due to increased pentylenetetrazol (PTZ)-induced neurotoxicity in SH-SY5Y cells were not clarified. Here, we investigated the role of VPA via modulation of TRPM2 channel on cell death and oxidative neurotoxicity in SH-SY5Y cells. The SH-SY5Y cell toxicity model was constructed by treating SH-SY5Y cells with PTZ. The VPA and TRPM2 channel antagonist N-(p-amylcinnamoyl) anthranilic acid (ACA) were added to prevent neurotoxicity in PTZ-induced SH-SY5Y cells. The role of the VPA and TRPM2 channel was evaluated using an ELISA kit and patch-clamp. Primarily, antioxidant (GSH and GSH-Px) and oxidative stress (MDA and ROS) levels and inflammatory factors (IL-1β, IL-6, and TNF-α) in cells were determined by ELISA kits. Then, TRPM2 channel activation in cells was detected using both the ELISA kit and patch-clamp methods. In addition, apoptosis and cell viability levels in cells were determined by performing PARP1, caspase-3, caspase-9, and CCK-8 assays by ELISA kits. Our results showed that the TRPM2 channel is vital in damage formation in PTZ-induced cells. Furthermore, we observed that VPA attenuated PTZ-induced neurotoxicity by suppressing cells’ oxidative stress and inflammation, and reducing TRPM2 channel activation. In our study, in which the protective effect of VPA and the role of the TRPM2 channel in PTZ-induced SH-SY5Y cells were investigated for the first time, we can conclude that VPA treatment and TRPM2 channel blockade can suppress PTZ-induced neurotoxicity.

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Acknowledgements

This study was presented as an oral presentation to the 7th International Brain Research School organized on 27 June-03 July 2022, Isparta, Turkey, by Autor’s. https://dergipark.org.tr/tr/download/issue-file/60314. The results of the current study were summarized from a Ph.D. thesis of AA.

Funding

This work was supported by the Research Fund of Istanbul University. Project No. 38188.

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Authors and Affiliations

  1. Department of Biophysics, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey

    Adem Ahlatcı & Muhammet Bektaş

  2. Department of Biophysics, Faculty of Medicine, Van Yuzuncu Yil University, TR- 65080, Van, Turkey

    Kenan Yıldızhan

  3. Department of Medical Biology, Faculty of Medicine, Van Yuzuncu Yil University, Van, Turkey

    Yasin Tülüce

Authors
  1. Adem Ahlatcı
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  2. Kenan Yıldızhan
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  3. Yasin Tülüce
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  4. Muhammet Bektaş
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Contributions

M.B. and A.A. reviewed the current literature, formulated the hypothesis, and designed the project. Y.T. and K.Y. contributed to in vitro experimental studies. K.Y. contributed to patch-clamp, biochemistry analysis, and manuscript writing. All authors read and approve the manuscript, and all data were generated in-house and that no paper mill was used.

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Correspondence to Kenan Yıldızhan.

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Ahlatcı, A., Yıldızhan, K., Tülüce, Y. et al. Valproic Acid Attenuated PTZ-induced Oxidative Stress, Inflammation, and Apoptosis in the SH-SY5Y Cells via Modulating the TRPM2 Channel. Neurotox Res 40, 1979–1988 (2022). https://doi.org/10.1007/s12640-022-00622-3

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