ATF2/BAP1 Axis Mediates Neuronal Apoptosis After Subarachnoid Hemorrhage via P53 Pathway

Area of Science:

• Neuroscience
• Molecular Biology
• Pathology

Background:

• Neuronal apoptosis is critical in subarachnoid hemorrhage (SAH) brain injury.
• BRCA1-associated protein 1 (BAP1) is implicated in apoptosis in various diseases.
• The role of BAP1 in SAH-induced neuronal apoptosis remains unconfirmed.

Purpose of the Study:

• To investigate the role of BAP1 in neuronal apoptosis following SAH.
• To elucidate the molecular mechanisms underlying BAP1's function in SAH.

Main Methods:

• Detected BAP1 expression in cerebrospinal fluid using ELISA.
• Induced SAH in mice via endovascular perforation.
• Utilized lentiviral shRNA to inhibit BAP1 in the mouse cortex.
• Employed luciferase and coimmunoprecipitation assays to explore mechanisms.

Main Results:

• BAP1 expression was elevated in SAH patients' CSF and linked to poor outcomes.
• Activating transcription factor-2 (ATF2) regulated BAP1 promoter activity.
• BAP1 overexpression increased P53 stability and activity, promoting apoptosis.
• Inhibiting the BAP1/P53 axis reduced neurological deficits and apoptosis in SAH mice.

Conclusions:

• The neuronal ATF2/BAP1 axis contributes to brain damage in SAH by influencing P53.
• This axis represents a potential therapeutic target for SAH treatment.