ATF2/BAP1 Axis Mediates Neuronal Apoptosis After Subarachnoid Hemorrhage via P53 Pathway.
Stroke
; 55(8): 2113-2125, 2024 Aug.
Article
en En
| MEDLINE
| ID: mdl-38965653
ABSTRACT
BACKGROUND:
Neuronal apoptosis plays an essential role in the pathogenesis of brain injury after subarachnoid hemorrhage (SAH). BAP1 (BRCA1-associated protein 1) is considered to exert pro-apoptotic effects in multiple diseases. However, evidence supporting the effect of BAP1 on the apoptotic response to SAH is lacking. Therefore, we aimed to confirm the role of BAP1 in SAH-induced apoptosis.METHODS:
Enzyme-linked immunosorbent assay (ELISA) was used to detect BAP1 expression in the cerebrospinal fluid. Endovascular perforation was performed in mice to induce SAH. Lentiviral short hairpin RNA targeting BAP1 mRNA was transduced into the ipsilateral cortex of mice with SAH to investigate the role of BAP1 in neuronal damage. Luciferase and coimmunoprecipitation assays were performed to investigate the mechanism through which BAP1 participates in hemin-induced SAH.RESULTS:
First, BAP1 expression was upregulated in the cerebrospinal fluid of patients with SAH and positively associated with unfavorable outcomes. ATF2 (activating transcription factor-2) then regulated BAP1 expression by binding to the BAP1 promoter. In addition, BAP1 overexpression enhanced P53 activity and stability by reducing P53 proteasome-mediated degradation. Subsequently, elevated P53 promoted neuronal apoptosis via the P53 pathway. Inhibition of the neuronal BAP1/P53 axis significantly reduced neurological deficits and neuronal apoptosis and improved neurological dysfunction in mice after SAH.CONCLUSIONS:
Our results suggest that the neuronal ATF2/BAP1 axis exerts a brain-damaging effect by modulating P53 activity and stability and may be a novel therapeutic target for SAH.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Hemorragia Subaracnoidea
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Proteína p53 Supresora de Tumor
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Apoptosis
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Proteínas Supresoras de Tumor
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Ubiquitina Tiolesterasa
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Neuronas
Límite:
Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Stroke
Año:
2024
Tipo del documento:
Article
País de afiliación:
China