Increases in reactive oxygen species enhance vascular endothelial cell migration through a mechanism dependent on the transient receptor potential melastatin 4 ion channel

Daniela Sarmiento, Ignacio Montorfano, Oscar Cerda, Mónica Cáceres, Alvaro Becerra, Claudio Cabello-Verrugio, Alvaro A. Elorza, Claudia Riedel, Pablo Tapia, Luis A. Velásquez, Diego Varela, Felipe Simon

Resultado de la investigación: Article

22 Citas (Scopus)

Resumen

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 cell migration 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 potential melastatin 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.We demonstrate 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.

Idioma originalEnglish
Páginas (desde-hasta)187-196
Número de páginas10
PublicaciónMicrovascular Research
Volumen98
DOI
EstadoPublished - 1 mar 2015

Huella dactilar

Endothelial cells
Oxidative stress
Ion Channels
Cell Movement
Reactive Oxygen Species
Endothelial Cells
Oxidative Stress
Calcium Channels
Inflammation
Inflammation Mediators
Monolayers
Pharmacology
Tissue

ASJC Scopus subject areas

  • Biochemistry
  • Cardiology and Cardiovascular Medicine
  • Cell Biology

Citar esto

Sarmiento, Daniela ; Montorfano, Ignacio ; Cerda, Oscar ; Cáceres, Mónica ; Becerra, Alvaro ; Cabello-Verrugio, Claudio ; Elorza, Alvaro A. ; Riedel, Claudia ; Tapia, Pablo ; Velásquez, Luis A. ; Varela, Diego ; Simon, Felipe. / Increases in reactive oxygen species enhance vascular endothelial cell migration through a mechanism dependent on the transient receptor potential melastatin 4 ion channel. En: Microvascular Research. 2015 ; Vol. 98. pp. 187-196.
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abstract = "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 cell migration 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 potential melastatin 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.We demonstrate 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.",
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Increases in reactive oxygen species enhance vascular endothelial cell migration through a mechanism dependent on the transient receptor potential melastatin 4 ion channel. / Sarmiento, Daniela; Montorfano, Ignacio; Cerda, Oscar; Cáceres, Mónica; Becerra, Alvaro; Cabello-Verrugio, Claudio; Elorza, Alvaro A.; Riedel, Claudia; Tapia, Pablo; Velásquez, Luis A.; Varela, Diego; Simon, Felipe.

En: Microvascular Research, Vol. 98, 01.03.2015, p. 187-196.

Resultado de la investigación: Article

TY - JOUR

T1 - Increases in reactive oxygen species enhance vascular endothelial cell migration through a mechanism dependent on the transient receptor potential melastatin 4 ion channel

AU - Sarmiento, Daniela

AU - Montorfano, Ignacio

AU - Cerda, Oscar

AU - Cáceres, Mónica

AU - Becerra, Alvaro

AU - Cabello-Verrugio, Claudio

AU - Elorza, Alvaro A.

AU - Riedel, Claudia

AU - Tapia, Pablo

AU - Velásquez, Luis A.

AU - Varela, Diego

AU - Simon, Felipe

PY - 2015/3/1

Y1 - 2015/3/1

N2 - 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 cell migration 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 potential melastatin 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.We demonstrate 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.

AB - 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 cell migration 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 potential melastatin 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.We demonstrate 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.

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