Lactylation of histone by BRD4 regulates astrocyte polarization after experimental subarachnoid hemorrhage.
J Neuroinflammation
; 21(1): 186, 2024 Jul 30.
Article
en En
| MEDLINE
| ID: mdl-39080649
ABSTRACT
Under subarachnoid hemorrhage (SAH) conditions, astrocytes undergo a marked intensification of glycolytic activity, resulting in the generation of substantial amounts of lactate to maintain the energy demand for neurons and other brain cells. Lactate has garnered increasing attention in recent years because of its emerging role in critical biological processes such as inflammation regulation and neuroprotection, particularly through its histone lactylation. Bromodomain-containing protein 4 (BRD4) plays a crucial role in maintaining neural development and promoting memory formation in the central nervous system. Nonetheless, the function and regulatory mechanism of BRD4 and histone lactylation in astrocytes following SAH remain elusive. Our findings indicate that BRD4, a crucial epigenetic regulator, plays a definitive role in histone lactylation. Both in vitro and in vivo, these results demonstrated that targeted silencing of BRD4 in astrocytes can significantly reduce H4K8la lactylation, thereby aggravating the A1 polarization of astrocytes and ultimately affecting the recovery of neural function and prognosis in mice after SAH. In summary, BRD4 plays a pivotal role in modulating astrocyte polarization following SAH via histone lactylation. Targeting this mechanism might offer an efficient therapeutic strategy for SAH.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Hemorragia Subaracnoidea
/
Factores de Transcripción
/
Histonas
/
Astrocitos
/
Proteínas que Contienen Bromodominio
Idioma:
En
Revista:
J Neuroinflammation
Asunto de la revista:
NEUROLOGIA
Año:
2024
Tipo del documento:
Article