Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Dual Aquaporin and Sigma1 Receptor (DAS) Modulators: New Tools for Counteracting Oxidative Stress

Version 1 : Received: 10 November 2020 / Approved: 12 November 2020 / Online: 12 November 2020 (09:33:34 CET)

How to cite: Pellavio, G.; Rossino, G.; Gastaldi, G.; Rossi, D.; Linciano, P.; Collina, S.; Laforenza, U. Dual Aquaporin and Sigma1 Receptor (DAS) Modulators: New Tools for Counteracting Oxidative Stress. Preprints 2020, 2020110333 (doi: 10.20944/preprints202011.0333.v1). Pellavio, G.; Rossino, G.; Gastaldi, G.; Rossi, D.; Linciano, P.; Collina, S.; Laforenza, U. Dual Aquaporin and Sigma1 Receptor (DAS) Modulators: New Tools for Counteracting Oxidative Stress. Preprints 2020, 2020110333 (doi: 10.20944/preprints202011.0333.v1).

Abstract

Specific aquaporins (AQP), called peroxyporins, play a relevant role in controlling H2O2 permeability and ensure reactive oxygen species wasting during oxidative stress. Another target involved in oxidative stress is the Sigma1 Receptor (S1R), since its activation is triggered by oxidative or endoplasmic reticulum stress. Herein we evaluated the effect of S1R modulators on AQP-dependent water permeability in the presence and in the absence of oxidative stress. Applying stopped-flow light scattering and fluorescent probe methods, water and hydrogen peroxide permeability in Hela cells have been studied. Results evidenced that S1R agonists can restore water permeability in heat-stressed cells and the co-administration with a S1R antagonist totally counteracted the ability to restore the water permeability. All compounds except one were able to counteract the oxidative stress of HeLa cells specifically knocked down for S1R. Taken together, our results support the hypothesis that the investigated compounds act as dual aquaporin and Sigma1 receptor (DAS) modulators. The finding that small molecules can modulate both AQP and S1R opens a new direction toward the identification of innovative drugs able to regulate cell survival during oxidative stress in pathologic conditions, like cancer and degenerative diseases.

Subject Areas

peroxiporins; oxidative stress; hydrogen peroxide; water channels; Sigma1 receptors; Sigma1 receptor modulators; neurodegenerative diseases

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