Figure 5.

GPX4 regulates necroinflammation by inhibiting TNF-α-mediated NF-κB signaling. TNF-α regulates cell survival and death by activating the key transcription factor of NF-κB. NF-κB signal activation, as a downstream promoter element of TNF-α, is negatively suppressed in intracellular survival signaling. Inversely, TNF-α-mediated NF-κB signaling can be markedly activated when ROS is produced in mitochondria. GPX4 can attenuate the necroinflammatory response and suppress the inflammatory cytokines by down-regulating TNF-α-mediated NF-κB signaling pathway. ROS, reactive oxygen species; GPX4, glutathione peroxidase 4; GSH, glutathione; GSSG, glutathione disulfide; FAD/FADH, flavin adenine dinucletide; NADP/NADPH, nicotinamide adenine dinucleotide phosphate; NF-KB, nuclear factor κB; IκBα, inhibitor of NF-κB α; TNF-α, tumor necrosis factor-α; LT, leukotriene; COX, cyclooxygenase; NOS, nitric oxide synthase.