Glutathione Peroxidase 4 in Blunt Snout Bream (Megalobrama amblycephala) Regulates Ferroptosis and Inflammation in Response to Aeromonas hydrophila Infection

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Glutathione peroxidase 4 (GPX4) plays a crucial role in regulating lipid peroxidation and is associated with infection and inflammation, particularly in terms of its effects on inflammatory cytokines and ferroptosis. This study aimed to investigate the regulatory effects of Gpx4 on the inflammatory response and ferroptosis in blunt snout bream (Megalobrama amblycephala), a significant freshwater fish species in China, after Aeromonas hydrophila infection. Using a bioinformatics analysis, we discovered that Gpx4 has a conserved protein structure and high amino acid identity in various carp species, indicating functional conservation across species and through involution. RT-qPCR analysis revealed that gpx4 mRNA increased after the neuroembryonic stage during early development and was particularly highly expressed in the liver of healthy adult fish. Upon A. hydrophila infection, gpx4 expression decreased significantly and rapidly in the liver. In L8824 cells, overexpression of gpx4 suppressed inflammatory cytokines and inhibited ferroptosis in response to both A. hydrophila infection and induction of ferroptosis-inducer RSL3. These findings highlight the regulatory role of Gpx4 in cellular ferroptosis and inflammation, providing insights into the complex mechanisms of disease resistance and potentially aiding in the development of strategies for disease control in fish.

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