SP1-Induced GLS2 Promotes Hypoxia/Reoxygenation-Induced AC16 Cell Injury by Regulating Ferroptosis Via an AMPK/mTOR...

Area of Science:

• Cardiovascular Biology
• Cell Death Mechanisms
• Molecular Cardiology

Background:

• Myocardial ischemia-reperfusion injury (MIRI) is a major cause of mortality in acute myocardial infarction (AMI).
• Glutaminase 2 (GLS2) is implicated in cardiomyocyte ferroptosis, but its role in MIRI remains unclear.

Purpose of the Study:

• To investigate the role and mechanism of GLS2 in MIRI.
• To explore GLS2 as a potential therapeutic target for MIRI.

Main Methods:

• In vitro: MTT, flow cytometry, Western blot, ELISA, iron assay, GSH, MDA, ROS assays.
• In vivo: Mouse MI model.
• Molecular techniques: ChIP, dual-luciferase reporter assays, SP1 and GLS2 knockdown, AMPK inhibitor.

Main Results:

• Ischemia/reperfusion induced cardiomyocyte apoptosis, inflammation, and ferroptosis.
• GLS2 knockdown alleviated hypoxia/reoxygenation-induced injury and ferroptosis.
• SP1 upregulated GLS2 transcription; SP1 silencing activated AMPK/mTOR pathway.
• GLS2 silencing repressed myocardial damage in vivo.

Conclusions:

• SP1-activated GLS2 exacerbates MIRI by promoting ferroptosis via inactivating the AMPK/mTOR pathway.
• Targeting GLS2 presents a promising therapeutic strategy for MIRI.