EMP1 knockdown mitigated high glucose-induced pyroptosis and oxidative stress in rat H9c2 cardiomyocytes by...

Area of Science:

• Cardiology
• Molecular Biology
• Cell Biology

Background:

• Diabetic cardiomyopathy is a significant complication of diabetes.
• High glucose (HG) induces cardiac cell pyroptosis and oxidative injury.
• The precise mechanisms underlying HG-induced cardiac damage require further elucidation.

Purpose of the Study:

• To investigate the role of EMP1 in high glucose-induced pyroptosis and oxidative injury in H9c2 cardiac cells.
• To explore the underlying molecular mechanisms, including the RAS/RAF/MAPK pathway.

Main Methods:

• H9c2 cells were exposed to high glucose (33 mM) to induce cytotoxicity.
• EMP1 knockdown was achieved using EMP1-siRNA.
• Cell proliferation, apoptosis, pyroptosis markers (NLRP3, IL-1β, ASC, GSDMD, cleaved-caspase1, cleaved-caspase3), mitochondrial damage, and oxidative stress were assessed.
• RAS/RAF/MAPK signaling pathway activation was investigated.

Main Results:

• EMP1 knockdown rescued cell proliferation inhibited by HG.
• EMP1 siRNA significantly reduced apoptosis and pyroptosis in HG-treated cells.
• EMP1 knockdown alleviated mitochondrial damage and oxidative stress.
• NLRP3 activation reversed the protective effects of EMP1 knockdown.
• EMP1 knockdown suppressed the RAS/RAF/MAPK pathway; RAS overexpression counteracted the protective effects of EMP1 knockdown.

Conclusions:

• EMP1 plays a critical role in high glucose-induced pyroptosis and oxidative injury in H9c2 cells.
• EMP1 knockdown exerts protective effects by inhibiting pyroptosis, oxidative stress, and mitochondrial damage, partly via the RAS/RAF/MAPK pathway.
• EMP1 inhibition represents a potential therapeutic target for diabetic cardiomyopathy.