ABCG2 shields against epilepsy, relieves oxidative stress and apoptosis via inhibiting the ISGylation of STAT1 and mTOR.
Redox Biol
; 75: 103262, 2024 09.
Article
en En
| MEDLINE
| ID: mdl-38981367
ABSTRACT
The transporter protein ABC subfamily G member 2 (ABCG2) is implicated in epilepsy; however, its specific role remains unclear. In this study, we assessed changes in ABCG2 expression and its role in epilepsy both in vitro and in vivo. We observed an instantaneous increase in ABCG2 expression in epileptic animals and cells. Further, ABCG2 overexpression significantly suppressed the oxidative stress and apoptosis induced by glutamate, kainic acid (KA), and lipopolysaccharide (LPS) in neuronal and microglia cells. Furthermore, inhibiting ABCG2 activity offset this protective effect. ABCG2-deficient mice (ABCG2-/-) showed shorter survival times and decreased survival rates when administered with pentylenetetrazole (PTZ). We also noticed the accumulation of signal transducer and activator of transcription 1 (STAT1) and decreased phosphorylation of mammalian target of rapamycin kinase (mTOR) along with increased ISGylation in ABCG2-/- mice. ABCG2 overexpression directly interacted with STAT1 and mTOR, leading to a decrease in their ISGylation. Our findings indicate the rapid increase in ABCG2 expression acts as a shield in epileptogenesis, indicating ABCG2 may serve as a potential therapeutic target for epilepsy treatment.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Apoptosis
/
Epilepsia
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Factor de Transcripción STAT1
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Serina-Treonina Quinasas TOR
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Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Redox Biol
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Países Bajos