4-Hydroxy-Trans-2-Nonenal in the Regulation of Anti-Oxidative and Pro-Inflammatory Signaling Pathways

Figure 4

Role of HNE on NF-κB-mediated pro-inflammatory signaling: During oxidative stress conditions ROS activate a series of protein kinases such as IKK which phosphorylates IkBα leading to dissociation of the inactive complex of NF-κB-IκBα. The active NF-κB is translocated to the nucleus and binds to its consensus sequences to induce the transcription of target genes. HNE exerts pleiotropic effects on NF-κB; (a) the low concentrations of HNE (<5 μM) could activate NF-κB whereas (b) high concentrations (>5 μM) of HNE could inhibit NF-κB. HNE could modulate NF-κB activity by interacting with upstream protein kinases and can directly modify NF-κB subunits.

(a)

(b)