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Myocardial ischemia/reperfusion injury (MIRI) is related to ferroptosis and apoptosis elicited by reactive oxygen species (ROS). In this research, we investigated the protective effect of salvianolic acid B (SAB) as a natural antioxidant on ferroptosis and apoptosis in the MIRI process, and discussed the protective mechanism inhibiting ubiquitin-proteasome degradation of glutathione peroxidase 4 (GPX4) and the c-Jun N-terminal kinases (JNK) apoptosis signal pathway. We observed that ferroptosis and apoptosis occurred in the MIRI rat model in vivo and the H9c2 cardiomyocyte hypoxia/reoxygenation (H/R) damage model in vitro. SAB can alleviate tissue damage related to ROS, ferroptosis and apoptosis. Ubiquitin-proteasome degradation of GPX4 occurred in H/R models, and SAB reduced the ubiquitin-proteasome degradation of GPX4. SAB downregulates JNK phosphorylation and the expression of BCL2-Associated X (Bax)/B-cell lymphoma-2 (Bcl-2) and Caspase-3 to inhibit apoptosis. The role of GPX4 in the cardioprotection of SAB was further verified by the elimination effect of the GPX4 inhibitor RAS-selective lethal 3 (RSL3). This research shows that SAB may be used as a myocardial protective agent against oxidative stress, ferroptosis and apoptosis, and has potential clinical application prospects. [ABSTRACT FROM AUTHOR]

The success of the pathogenic bacteria is partly attributable to their ability to thwart host innate immune responses, which includes resisting the antimicrobial functions of macrophages. And reactive oxygen species (ROS) is one of the most effective antimicrobial components of macrophages to kill invading bacteria. Our previous studies found that Aeromonas hydrophila can survive in fish macrophages, which suggested that this bacterium might take fish macrophages as their shelters to resist drug killings and other immune damage. But how A . hydrophila survive in host macrophages remains unknown. Since KatG has been reported to have not only catalase activity but also peroxidase and peroxynitritase activity, the amino acid sequence and protein structure of KatG was analyzed in this study, the function of KatG in A . hydrophila survival in and escape from host macrophages was also carried out. The bioinformatics analysis displayed that KatG of A . hydrophila B11 showed >93% homologous to that of KatG in other Aeromonas . KatG of A . hydrophila was stable silenced by shRNA and RT-qPCR confirmed the expression of KatG in KatG -RNAi was significantly reduced. The survival rate of intracellular KatG -RNAi decreased by 80% compared to that of the wild type strain B11, while the intracellular ROS level of the macrophages that phagocytosed KatG -RNAi increased 65.9% when compared to that of the macrophages phagocytosed wild-type strain. The immune escape rate of A . hydrophila decreased by 85% when the expression of KatG was inhibited. These results indicated that (1) The amino acid sequence and protein structure of KatG of A . hydrophila is conserved; (2) KatG helped A . hydrophila to survive in fish macrophages by eliminating the harm of intracellular H 2 O 2 and inhibiting intracellular ROS levels increased; (3) A small portion of intracellular A . hydrophila could escape from host macrophages for further infection, in this process KatG also played important role. [ABSTRACT FROM AUTHOR]