TRPM7 underlies cadmium cytotoxicity in pulmonary cells DOI Creative Commons
Leonor Correia, Alexey Shalygin,

Anna Erbacher

et al.

Archives of Toxicology, Journal Year: 2025, Volume and Issue: unknown

Published: May 15, 2025

TRPM7 is a kinase-coupled ion channel that exhibits high activity in the immune and epithelial cells of different organs, including lung. Electrophysiological studies have established displays permeability to Mg2+, Zn2+, Ca2+, as well trace metal cations. While critical role cellular balance Ca2+ well-documented, its contribution uptake cations, frequent respiratory pollutants, remains unclear. Here, we performed an electrophysiological assessment pulmonary A549 revealing endogenous currents, which were eliminated by knockout (KO) gene using CRISPR/Cas9 approach or administration NS8593 VER155008, two structurally unrelated inhibitors channel. Unlike prior with various cell lines showing KO mutation induces growth arrest, observed maintained normal viability after genetic pharmacological inactivation TRPM7. Consequently, used examine impact Cd2+ on found both agents mitigated cytotoxicity. Analogous cells, analysis mouse primary alveolar type 2 (ATII) revealed currents exposure reduced ATII TRPM7-dependent fashion. Hence, contributes cytotoxicity can serve therapeutic target alleviate toxic effects exposure.

Language: Английский

TRPM7 underlies cadmium cytotoxicity in pulmonary cells DOI Creative Commons
Leonor Correia, Alexey Shalygin,

Anna Erbacher

et al.

Archives of Toxicology, Journal Year: 2025, Volume and Issue: unknown

Published: May 15, 2025

TRPM7 is a kinase-coupled ion channel that exhibits high activity in the immune and epithelial cells of different organs, including lung. Electrophysiological studies have established displays permeability to Mg2+, Zn2+, Ca2+, as well trace metal cations. While critical role cellular balance Ca2+ well-documented, its contribution uptake cations, frequent respiratory pollutants, remains unclear. Here, we performed an electrophysiological assessment pulmonary A549 revealing endogenous currents, which were eliminated by knockout (KO) gene using CRISPR/Cas9 approach or administration NS8593 VER155008, two structurally unrelated inhibitors channel. Unlike prior with various cell lines showing KO mutation induces growth arrest, observed maintained normal viability after genetic pharmacological inactivation TRPM7. Consequently, used examine impact Cd2+ on found both agents mitigated cytotoxicity. Analogous cells, analysis mouse primary alveolar type 2 (ATII) revealed currents exposure reduced ATII TRPM7-dependent fashion. Hence, contributes cytotoxicity can serve therapeutic target alleviate toxic effects exposure.

Language: Английский

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