Ouabain’s Influence on TRPV4 Channels of Epithelial Cells: An Exploration of TRPV4 Activity, Expression, and Signaling Pathways
-
Published:2023-11-24
Issue:23
Volume:24
Page:16687
-
ISSN:1422-0067
-
Container-title:International Journal of Molecular Sciences
-
language:en
-
Short-container-title:IJMS
Author:
Ponce Arturo1, Larre Isabel23, Jimenez Lidia1, Roldán Maria Luisa1, Shoshani Liora1, Cereijido Marcelino1
Affiliation:
1. Department of Physiology, Biophysics and Neurosciences, CINVESTAV-IPN, Mexico City 07360, Mexico 2. Department of Physiology, Faculty of Medicine, Universidad Nacional Autónoma de Mexico (UNAM), Mexico City 04510, Mexico 3. Department of Clinical and Translational Science, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA
Abstract
Ouabain, a substance originally obtained from plants, is now classified as a hormone because it is produced endogenously in certain animals, including humans. However, its precise effects on the body remain largely unknown. Previous studies have shown that ouabain can influence the phenotype of epithelial cells by affecting the expression of cell–cell molecular components and voltage-gated potassium channels. In this study, we conducted whole-cell clamp assays to determine whether ouabain affects the activity and/or expression of TRPV4 channels. Our findings indicate that ouabain has a statistically significant effect on the density of TRPV4 currents (dITRPV4), with an EC50 of 1.89 nM. Regarding treatment duration, dITRPV4 reaches its peak at around 1 h, followed by a subsequent decline and then a resurgence after 6 h, suggesting a short-term modulatory effect related to on TRPV4 channel activity and a long-term effect related to the promotion of synthesis of new TRPV4 channel units. The enhancement of dITRPV4 induced by ouabain was significantly lower in cells seeded at low density than in cells in a confluent monolayer, indicating that the action of ouabain depends on intercellular contacts. Furthermore, the fact that U73122 and neomycin suppress the effect caused by ouabain in the short term suggests that the short-term induced enhancement of dITRPV4 is due to the depletion of PIP2 stores. In contrast, the fact that the long-term effect is inhibited by PP2, wortmannin, PD, FR18, and IKK16 suggests that cSrc, PI3K, Erk1/2, and NF-kB are among the components included in the signaling pathways.
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Reference98 articles.
1. Plants and cardiac glycosides;Hollman;Br. Heart J.,1985 2. Bejček, J., Jurášek, M., Spiwok, V., and Rimpelová, S. (2021). Quo vadis Cardiac Glycoside Research?. Toxins, 13. 3. A review of cardiac glycosides: Structure, toxicokinetics, clinical signs, diagnosis and antineoplastic potential;Botelho;Toxicon,2018 4. Plant-derived cardiac glycosides: Role in heart ailments and cancer management;Patel;Biomed. Pharmacother.,2016 5. Ouabain—The key to cardioprotection?;Fuerstenwerth;Am. J. Ther.,2014
|
|