Baicalin Attenuates Diabetic Cardiomyopathy In Vivo and In Vitro by Inhibiting Autophagy and Cell Death Through...

Area of Science:

• Biochemistry
• Cardiovascular Biology
• Molecular Medicine

Background:

• Diabetic cardiomyopathy (DCM) involves cardiomyocyte death, significantly impacting health.
• Baicalin (BAI) is a bioactive compound with known cardiovascular benefits.
• Sentrin/SUMO-specific protease 1 (SENP1) regulates Sirtuin 3 (SIRT3) deSUMOylation, crucial for mitochondrial quality control and cell protection.

Purpose of the Study:

• To investigate if BAI enhances mitochondrial quality control and prevents cell death in DCM by modulating SIRT3 deSUMOylation through SENP1.
• To elucidate the molecular mechanisms underlying BAI's cardioprotective effects in the context of DCM.

Main Methods:

• Utilized high glucose-induced cardiomyocytes and db/db mice models.
• Performed gene silencing and overexpression of SENP1.
• Employed co-immunoprecipitation to assess SIRT3 SUMOylation levels.
• Analyzed mitochondrial protein acetylation, reactive oxygen species accumulation, autophagy, oxidative phosphorylation, and cell death.

Main Results:

• SENP1 expression was reduced in high glucose-induced cardiomyocytes and db/db mice.
• Silencing SENP1 abolished BAI's cardioprotective effects, while SENP1 overexpression mimicked them.
• BAI inhibited SIRT3 SUMOylation via SENP1, preventing mitochondrial dysfunction and cell death.
• Inhibition of SENP1 led to increased SIRT3 SUMOylation, mitochondrial damage, and cell death, which BAI could not reverse.

Conclusions:

• BAI improves DCM by promoting SIRT3 deSUMOylation through SENP1, thereby restoring mitochondrial stability and preventing cardiomyocyte death.
• This study identifies SIRT3 SUMOylation as a key factor in DCM development.
• BAI demonstrates cardioprotective effects against ferroptosis and apoptosis in DCM by targeting the SENP1 pathway.