Carvedilol Reduces the Neuronal Apoptosis after Ischemic Stroke by Modulating Activator of Transcription 3 Expression...

Area of Science:

• Neuroscience
• Molecular Biology
• Biochemistry

Background:

• Cerebral ischemia, encompassing local and diffuse types, presents diverse etiologies but unclear underlying mechanisms.
• Identifying key molecular players is crucial for understanding and treating ischemic conditions.

Purpose of the Study:

• To investigate the role of activator of transcription 3 (ATF3) as a hub gene in cerebral ischemia.
• To explore the therapeutic potential of Carvedilol targeting ATF3 in an in vitro model of ischemia.

Main Methods:

• Bioinformatics analysis to identify hub genes in ischemia.
• In vitro cell culture using PC12 cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R).
• Assessment of cell viability, apoptosis, and expression of key proteins (Bax, Bcl-2, cleaved caspase-3) following genetic manipulation of ATF3 and Carvedilol treatment.

Main Results:

• ATF3 was identified as a hub gene and its expression increased in OGD/R-treated PC12 cells.
• ATF3 deficiency impaired cell viability and promoted apoptosis, while overexpression had opposite effects.
• Carvedilol treatment enhanced cell viability and reduced apoptosis in OGD/R-PC12 cells.
• Carvedilol's protective effects were diminished by ATF3 deficiency.
• Carvedilol and siATF3 treatment modulated Bax, Bcl-2, and cleaved caspase-3 expression.

Conclusions:

• ATF3 plays a significant role in regulating cell viability and apoptosis in the context of cerebral ischemia.
• Carvedilol demonstrates neuroprotective effects by targeting ATF3, potentially through modulation of apoptosis-related proteins.
• Carvedilol represents a promising therapeutic agent for cerebral ischemia by inhibiting ATF3 activity.