PM2.5-Induced Cardiac Structural Modifications and Declined Pro-Survival Signalling Pathways Are Responsible for the Inefficiency of GSK-3β Inhibitor in Attenuating Myocardial Ischemia-Reperfusion Injury in Rats.

Abstract

Circulatory GSK3β is recognized as a biomarker and therapeutic target for diseases, including myocardial diseases. However, its potential as a target for myocardial ischemia-reperfusion injury (IR) in the presence of PM2.5 exposure is unclear. Wistar rats underwent IR following either a 21-day or single exposure to PM2.5 at a concentration of 250 µg/m3. The effects of GSK3β inhibitor on cardiac physiology, tissue injury, mitochondrial function, and the PI3K/AKT/GSK3β signalling axis were examined. The inhibitor was not effective in improving hemodynamics or reducing IR-induced infarction in the myocardium exposed to PM2.5 for 21 days. However, for a single-day exposure, the inhibitor showed potential in mitigating cardiac injury. In normal hearts undergoing IR, the inhibitor activated the PI3K/AKT signalling pathway, improved mitochondrial function, and reduced oxidative stress. These positive effects were not observed in PM2.5-exposed rats. Furthermore, the inhibitor stimulated autophagy in hearts exposed to PM2.5 for 21 days and subjected to IR, resulting in increased mTOR expression and decreased AMPK expression. In normal hearts and those exposed to a single dose of PM2.5, the inhibitor effectively activated the PI3K/Akt/AMPK axis. These findings suggest that GSK3β may not be a reliable therapeutic target for IR in the presence of chronic PM2.5 exposure.

• Authors: Bhavana Sivakumar, Nemat Ali, Sheikh F Ahmad, Ahmed Nadeem, Mohammad Waseem, Gino A Kurian
• Journal: Cells (Cells) Vol. 12 Issue 16 (08 15 2023) ISSN: 2073-4409 [Electronic] Switzerland
• PMID: 37626874 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glycogen Synthase Kinase 3 beta
• AMP-Activated Protein Kinases
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt
• Particulate Matter

Topics

• Rats
• Animals
• Myocardial Reperfusion Injury (drug therapy)
• Glycogen Synthase Kinase 3 beta
• Rats, Wistar
• AMP-Activated Protein Kinases
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt
• Particulate Matter (toxicity)