ERO1α primes the ryanodine receptor to respond to arsenite with concentration dependent Ca2+ release sequentially triggering two different mechanisms of ROS formation.
Chem Biol Interact
; 383: 110694, 2023 Sep 25.
Article
em En
| MEDLINE
| ID: mdl-37659621
ABSTRACT
A 6 h exposure of U937 cells to 2.5 µM arsenite stimulates low Ca2+ release from the inositol 1, 4, 5-triphosphate receptor (IP3R), causing a cascade of causally connected events, i.e., endoplasmic reticulum oxidoreductin-1α (ERO1α) expression, activation of the ryanodine receptor (RyR), mitochondrial Ca2+ accumulation, mitochondrial superoxide formation and further ERO1α expression. At greater arsenite concentrations, the release of the cation from the IP3R and the ensuing ERO1α expression remained unchanged but were nevertheless critical to sequentially promote concentration-dependent increases in Ca2+ release from the RyR, NADPH oxidase activation and a third mechanism of ERO1α expression which, in analogy to the one driven by mitochondrial superoxide, was also mediated by reactive oxygen species (ROS) and devoid of effects on Ca2+ homeostasis. Thus, concentration-independent stimulation of Ca2+ release from the IP3R is of pivotal importance for the effects of arsenite on Ca2+ homeostasis. It stimulates the expression of a fraction of ERO1α that primes the RyR to respond to the metalloid with concentration-dependent Ca2+-release, triggering the formation of superoxide in the mitochondrial respiratory chain and via NADPH oxidase activation. The resulting dose-dependent ROS formation was associated with a progressive increase in ERO1α expression, which however failed to affect Ca2+ homeostasis, thereby suggesting that ROS, unlike IP3R-dependent Ca2+ release, promote ERO1α expression in sites distal from the RyR.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Espécies Reativas de Oxigênio
/
Arsenitos
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Canal de Liberação de Cálcio do Receptor de Rianodina
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article