Role of the TRPM4 channel in mitochondrial function, calcium release, and ROS generation in oxidative stress.
Biochem Biophys Res Commun
; 566: 190-196, 2021 08 20.
Article
en En
| MEDLINE
| ID: mdl-34144257
ABSTRACT
Ischemic heart disease is one of the most common causes of death worldwide. Mitochondrial dysfunction, excessive reactive oxygen species (ROS) generation, and calcium (Ca2+) overload are three key factors leading to myocardial death during ischemia-reperfusion (I/R) injury. Inhibition of TRPM4, a Ca2+-activated nonselective cation channel, protects the rat heart from I/R injury, but the specific mechanism underlying this effect is unclear. In this study, we investigated the mechanism of cardioprotection against I/R injury via TRPM4 using hydrogen peroxide (H2O2), a major contributor to oxidative stress, as an I/R injury model. We knocked out the TRPM4 gene in the rat cardiomyocyte cell line H9c2 using CRISPR/Cas9. Upon H2O2 treatment, intracellular Ca2+ level and ROS production increased in wild type (WT) cells but not in TRPM4 knockout (TRPM4KO) cells. With this treatment, two indicators of mitochondrial function, mitochondrial membrane potential (ΔΨm) and intracellular ATP levels, decreased in WT but not in TRPM4KO cells. Taken together, these findings suggest that blockade of the TRPM4 channel might protect the myocardium from oxidative stress by maintaining the mitochondrial membrane potential and intracellular ATP levels, possibly through preventing aberrant increases in intracellular Ca2+ and ROS.
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Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Calcio
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Especies Reactivas de Oxígeno
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Miocitos Cardíacos
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Canales Catiónicos TRPM
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Mitocondrias Cardíacas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2021
Tipo del documento:
Article