Asbestos Fibers Enhance the TMEM16A Channel Activity in Xenopus Oocytes

Author:

Bernareggi Annalisa1ORCID,Zangari Martina1,Constanti Andrew2,Zacchi Paola3,Borelli Violetta3,Mangogna Alessandro4ORCID,Lorenzon Paola1ORCID,Zabucchi Giuliano3

Affiliation:

1. Department of Life Sciences, University of Trieste, Via Fleming 22, 34127 Trieste, Italy

2. Department of Pharmacology, UCL School of Pharmacy, 29/39 Brunswick Square, London WC1N 1AX, UK

3. Department of Life Sciences, University of Trieste, Via Valerio 28/1, 34127 Trieste, Italy

4. Institute for Maternal and Child Health—IRCCS Burlo Garofolo, Via Dell’Istria 65/1, 34137 Trieste, Italy

Abstract

Background: The interaction of asbestos fibers with target cell membranes is still poorly investigated. Here, we detected and characterized an enhancement of chloride conductance in Xenopus oocyte cell membranes induced by exposure to crocidolite (Croc) asbestos fibers. Methods: A two-microelectrode voltage clamp technique was used to test the effect of Croc fiber suspensions on outward chloride currents evoked by step membrane depolarization. Calcium imaging experiments were also performed to investigate the variation of ‘resting’ oocyte [Ca2+]i following asbestos exposure. Results: The increase in chloride current after asbestos treatment, was sensitive to [Ca2+]e, and to specific blockers of TMEM16A Ca2+-activated chloride channels, MONNA and Ani9. Furthermore, asbestos treatment elevated the ‘resting’ [Ca2+]i likelihood by increasing the cell membrane permeability to Ca2 in favor of a tonic activation of TMEME16A channels. Western blot analysis confirmed that TMEME16A protein was endogenously present in the oocyte cell membrane and absorbed by Croc. Conclusion: the TMEM16A channels endogenously expressed by Xenopus oocytes are targets for asbestos fibers and represent a powerful tool for asbestos–membrane interaction studies. Interestingly, TMEM16A channels are highly expressed in many types of tumors, including some asbestos-related cancers, suggesting them, for the first time, as a possible early target of crocidolite-mediated tumorigenic effects on target cell membranes.

Publisher

MDPI AG

Subject

Filtration and Separation,Chemical Engineering (miscellaneous),Process Chemistry and Technology

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