Cargando…

L-Carnitine Suppresses Transient Receptor Potential Vanilloid Type 1 Activation in Human Corneal Epithelial Cells

Tear film hyperosmolarity induces dry eye syndrome (DES) through transient receptor potential vanilloid type 1 (TRPV1) activation. L-carnitine is a viable therapeutic agent since it protects against this hypertonicity-induced response. Here, we investigated whether L-carnitine inhibits TRPV1 activat...

Descripción completa

Detalles Bibliográficos
Autores principales: Lucius, Alexander, Chhatwal, Sirjan, Valtink, Monika, Reinach, Peter S., Li, Aruna, Pleyer, Uwe, Mergler, Stefan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10380586/
https://www.ncbi.nlm.nih.gov/pubmed/37511574
http://dx.doi.org/10.3390/ijms241411815
_version_ 1785080232705785856
author Lucius, Alexander
Chhatwal, Sirjan
Valtink, Monika
Reinach, Peter S.
Li, Aruna
Pleyer, Uwe
Mergler, Stefan
author_facet Lucius, Alexander
Chhatwal, Sirjan
Valtink, Monika
Reinach, Peter S.
Li, Aruna
Pleyer, Uwe
Mergler, Stefan
author_sort Lucius, Alexander
collection PubMed
description Tear film hyperosmolarity induces dry eye syndrome (DES) through transient receptor potential vanilloid type 1 (TRPV1) activation. L-carnitine is a viable therapeutic agent since it protects against this hypertonicity-induced response. Here, we investigated whether L-carnitine inhibits TRPV1 activation by blocking heat- or capsaicin-induced increases in Ca(2+) influx or hyperosmotic stress-induced cell volume shrinkage in a human corneal epithelial cell line (HCE-T). Single-cell fluorescence imaging of calcein/AM-loaded cells or fura-2/AM-labeled cells was used to evaluate cell volume changes and intracellular calcium levels, respectively. Planar patch-clamp technique was used to measure whole-cell currents. TRPV1 activation via either capsaicin (20 µmol/L), hyperosmolarity (≈450 mosmol/L) or an increase in ambient bath temperature to 43 °C induced intracellular calcium transients and augmented whole-cell currents, whereas hypertonicity induced cell volume shrinkage. In contrast, either capsazepine (10 µmol/L) or L-carnitine (1–3 mmol/L) reduced all these responses. Taken together, L-carnitine and capsazepine suppress hypertonicity-induced TRPV1 activation by blocking cell volume shrinkage.
format Online
Article
Text
id pubmed-10380586
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-103805862023-07-29 L-Carnitine Suppresses Transient Receptor Potential Vanilloid Type 1 Activation in Human Corneal Epithelial Cells Lucius, Alexander Chhatwal, Sirjan Valtink, Monika Reinach, Peter S. Li, Aruna Pleyer, Uwe Mergler, Stefan Int J Mol Sci Article Tear film hyperosmolarity induces dry eye syndrome (DES) through transient receptor potential vanilloid type 1 (TRPV1) activation. L-carnitine is a viable therapeutic agent since it protects against this hypertonicity-induced response. Here, we investigated whether L-carnitine inhibits TRPV1 activation by blocking heat- or capsaicin-induced increases in Ca(2+) influx or hyperosmotic stress-induced cell volume shrinkage in a human corneal epithelial cell line (HCE-T). Single-cell fluorescence imaging of calcein/AM-loaded cells or fura-2/AM-labeled cells was used to evaluate cell volume changes and intracellular calcium levels, respectively. Planar patch-clamp technique was used to measure whole-cell currents. TRPV1 activation via either capsaicin (20 µmol/L), hyperosmolarity (≈450 mosmol/L) or an increase in ambient bath temperature to 43 °C induced intracellular calcium transients and augmented whole-cell currents, whereas hypertonicity induced cell volume shrinkage. In contrast, either capsazepine (10 µmol/L) or L-carnitine (1–3 mmol/L) reduced all these responses. Taken together, L-carnitine and capsazepine suppress hypertonicity-induced TRPV1 activation by blocking cell volume shrinkage. MDPI 2023-07-23 /pmc/articles/PMC10380586/ /pubmed/37511574 http://dx.doi.org/10.3390/ijms241411815 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lucius, Alexander
Chhatwal, Sirjan
Valtink, Monika
Reinach, Peter S.
Li, Aruna
Pleyer, Uwe
Mergler, Stefan
L-Carnitine Suppresses Transient Receptor Potential Vanilloid Type 1 Activation in Human Corneal Epithelial Cells
title L-Carnitine Suppresses Transient Receptor Potential Vanilloid Type 1 Activation in Human Corneal Epithelial Cells
title_full L-Carnitine Suppresses Transient Receptor Potential Vanilloid Type 1 Activation in Human Corneal Epithelial Cells
title_fullStr L-Carnitine Suppresses Transient Receptor Potential Vanilloid Type 1 Activation in Human Corneal Epithelial Cells
title_full_unstemmed L-Carnitine Suppresses Transient Receptor Potential Vanilloid Type 1 Activation in Human Corneal Epithelial Cells
title_short L-Carnitine Suppresses Transient Receptor Potential Vanilloid Type 1 Activation in Human Corneal Epithelial Cells
title_sort l-carnitine suppresses transient receptor potential vanilloid type 1 activation in human corneal epithelial cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10380586/
https://www.ncbi.nlm.nih.gov/pubmed/37511574
http://dx.doi.org/10.3390/ijms241411815
work_keys_str_mv AT luciusalexander lcarnitinesuppressestransientreceptorpotentialvanilloidtype1activationinhumancornealepithelialcells
AT chhatwalsirjan lcarnitinesuppressestransientreceptorpotentialvanilloidtype1activationinhumancornealepithelialcells
AT valtinkmonika lcarnitinesuppressestransientreceptorpotentialvanilloidtype1activationinhumancornealepithelialcells
AT reinachpeters lcarnitinesuppressestransientreceptorpotentialvanilloidtype1activationinhumancornealepithelialcells
AT liaruna lcarnitinesuppressestransientreceptorpotentialvanilloidtype1activationinhumancornealepithelialcells
AT pleyeruwe lcarnitinesuppressestransientreceptorpotentialvanilloidtype1activationinhumancornealepithelialcells
AT merglerstefan lcarnitinesuppressestransientreceptorpotentialvanilloidtype1activationinhumancornealepithelialcells