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Response of TRPM2 Channel to Hypercapnic Acidosis and Role of Zn, Se, and GSH

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Abstract

Hypercapnia can increase the production of reactive oxygen species (ROS) by inducing oxidative stress in cells. Transient receptor potential melastatin 2 (TRPM2) channel activation that is realized by ROS plays a critical role in the cellular mechanism. It was shown that antioxidants such as zinc (Zn), selenium (Se), and glutathione (GSH) can partake in the structures of enzymes and create a protective effect against oxidative stress. This study revealed the relationship between TRPM2 channel and hypercapnia, and the interaction of zinc, selenium, and glutathione. In our study, normoxia, hypercapnia, hypercapnia + Zn, hypercapnia + Se, and hypercapnia + GSH were created, in transfected HEK293 cells. The cells were exposed to normoxia or hypercapnia gasses in two different times (30 min and 60 min), while Zn, Se, and GSH were applied to the cells in the other groups before being exposed to the gas mixtures. The statistical evaluation showed a significant increase in lipid peroxidation (LPO) level and lactate dehydrogenase (LDH)% in the hypercapnia 30 min and 60 min groups, compared to the normoxia 30 min and 60 min groups, and an increase in LPO level and LDH% in the hypercapnia groups that Zn, Se, and GSH were applied. It was determined that in comparison with the normoxia 30 min and 60 min groups, the amount of inward Ca+2 current across TRPM2 channels and mean current density increased in the groups that were exposed to hypercapnia for 30 min and 60 min, while the same values significantly decreased in the hypercapnia groups that Zn, Se, and GSH were applied. Also, it was shown that oxidative stress rose as the duration of hypercapnia exposure increased. It was concluded that hypercapnia increased oxidative stress and caused cellular membrane damage, while the addition of Zn, Se, and GSH could protect the cell membrane from these damaging effects.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

The present work was supported by the Research Fund of Istanbul University. Project No: 50309.

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Authors and Affiliations

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

    D. Duzgun Ergun

  2. Department of Biophysics, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey

    D. Duzgun Ergun, N. Pastaci Ozsobaci & D. Ozcelik

  3. Department of Biophysics, Faculty of Medicine, Uskudar University, Istanbul, Turkey

    S. Dursun

  4. Department of Biophysics, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey

    M. Naziroglu

  5. Drug Discovery Unit, BSN Health, Analyses, Innovation, Consultancy, Organization, Agriculture, Industry LTD. Inc., Göller Bölgesi Teknokenti, Isparta, Turkey

    M. Naziroglu

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  1. D. Duzgun Ergun
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  4. M. Naziroglu
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Correspondence to D. Duzgun Ergun.

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Ergun, D.D., Dursun, S., Ozsobaci, N.P. et al. Response of TRPM2 Channel to Hypercapnic Acidosis and Role of Zn, Se, and GSH. Biol Trace Elem Res 200, 147–155 (2022). https://doi.org/10.1007/s12011-021-02652-y

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