Increases in reactive oxygen species enhance vascular endothelial cell migration through a mechanism dependent on the transient receptor potential melastatin 4 ion channel
Author
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Sarmiento, Daniela
Author
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Montorfano, Ignacio
Author
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Cerda Arancibia, Óscar
Author
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Cáceres, Mónica
Author
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Becerra, Álvaro
Author
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Cabello Verrugio, Claudio
Author
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Elorza, Alvaro A.
Author
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Riedel, Claudia
Author
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Tapia, Pablo
Author
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Velásquez, Luis A.
Author
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Varela, Diego
Author
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Simon, Felipe
Admission date
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2015-07-09T18:19:54Z
Available date
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2015-07-09T18:19:54Z
Publication date
dc.date.issued
2015
Cita de ítem
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Microvascular Research 98 (2015) 187–196
en_US
Identifier
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Doi.org/10.1016/j.mvr.2014.02.001
Identifier
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https://repositorio.uchile.cl/handle/2250/131886
General note
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Artículo de publicación ISI
en_US
Abstract
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A hallmark of severe inflammation is reactive oxygen species (ROS) overproduction induced by increased
inflammatory mediators secretion. During systemic inflammation, inflammation mediators circulating in the
bloodstream interact with endothelial cells (ECs) raising intracellular oxidative stress at the endothelial monolayer.
Oxidative stress mediates several pathological functions, including an exacerbated EC migration.
Because cellmigration critically depends on calcium channel-mediated Ca2+ influx, the molecular identification
of the calcium channel involved in oxidative stress-modulated EC migration has been the subject of intense
investigation.
The transient receptor potentialmelastatin 4 (TRPM4) protein is a ROS-modulated non-selective cationic channel
that performs several cell functions, including regulating intracellular Ca2+ overload and Ca2+ oscillation. This
channel is expressed in multiple tissues, including ECs, and contributes to the migration of certain immune cells.
However, whether the TRPM4 ion channel participates in oxidative stress-mediated EC migration is not known.
Herein, we investigate whether oxidative stress initiates or enhances EC migration and study the role played by
the ROS-modulated TRPM4 ion channel in oxidative stress-mediated EC migration.
Wedemonstrate that oxidative stress enhances, but does not initiate, EC migration in a dose-dependent manner.
Notably, we demonstrate that the TRPM4 ion channel is critical in promoting H2O2-enhanced EC migration.
These results show that TRPM4 is a novel pharmacological target for the possible treatment of severe inflammation
and other oxidative stress-mediated inflammatory diseases.
en_US
Patrocinador
dc.description.sponsorship
FONDECYT 1121078
(FS), 11121239 (OC), 1100995 (AE), 1130996 (CR), 1120380 (CCV),
1120240 (DV), and 1120712 (LAV).MillenniumInstitute on Immunology
and Immunotherapy P09-016-F (FS, AE, CR), Centro para el
Desarrollo de la Nanociencia y Nanotecnologia (CEDENNA); FB0807
(LAV). Association-Francaise Contre Les Myopathies AFM 16670
(CCV), UNAB-DI-281-13/R (CCV) and UNAB DI-209-12/N (FS, AE,CR).
Increases in reactive oxygen species enhance vascular endothelial cell migration through a mechanism dependent on the transient receptor potential melastatin 4 ion channel