MG53 Protects against Sepsis-Induced Myocardial Dysfunction by Upregulating Peroxisome Proliferator-Activated Receptor-α

Figure 8

Schematic of the proposed mechanism involved in the protective effects of MG53 on PPARα in SIMD rats. Sepsis caused the H-FABP released from cardiomyocyte plasma and downregulated MG53 and PPARα protein levels. Endogenously, ROS were overproduced resulting in the activation of the caspase-3-dependent apoptosis pathway. Also, large amounts of inflammatory cytokines (IL-1, IL-6, and TNF-α) were generated due to the activation of some proinflammatory pathways (such as NF-κB) after SIMD. The supplementation of MG53 upregulated PPARα, attenuated cardiomyocyte damage, and prevented H-FABP release. H-FABP facilitated FAs transfer and activated PPARα. PPARα exhibited an anti-inflammatory effect through the inhibition of proinflammatory signaling pathways, such as NF-κB. Also, PPARα heterodimerized with RXR, banded to PPRE, and then recruited RNA Pol II to regulate gene function to play a crucial part in antioxidant stress, antiapoptosis, and promoting FAs metabolism. RXR = retinoid X receptor; RNA Pol II = RNA polymerase II; PPRE = PPAR response element; FAs = fatty acids.