Peroxisome-proliferator-activated receptors regulate redox signaling in the cardiovascular system

Figure 1 Oxidative stress-induced signaling pathways affecting peroxisome-proliferator-activated receptor transcript and protein activity. Oxidative stress triggers activation of ERK1/2, platelet-derived growth factor (PDGF), and phosphatidylinositol 3-kinase (PI3K)/Akt resulting in increased transcription of peroxisome-proliferator-activated receptors (PPARs) as a defense mechanism. Oxidized lipids activate transcription and activation of PPARs. Oxidative stress increases p38 mitogen-activated protein kinase and 5’AMP-activated protein kinase (AMPK) resulting in the phosphorylation of PPAR proteins resulting in suppressed transcription of PPARs. NOX: Nicotinamide adenine dinucleotide phosphate oxidase; ROS: Reactive oxygen species.

Figure 2 Antioxidant mechanisms of peroxisome-proliferator-activated receptors. Peroxisome-proliferator-activated receptors (PPARs) activate antioxidant genes via transcriptional regulation by binding on PPAR response element (PPRE) of promoter region of target genes. PPARs suppress nuclear factor kappa-B (NF-κB)-light-chain-enhancer of activated B cells via interaction with p50 and p65 resulting in decreased inflammatory response and oxidative stress. PPARs suppress phosphatidylinositol 3-kinase (PI3K)/Akt/Rac1 signaling axis via activation of PTEN resulting in decreased reactive oxygen species (ROS). RXR: Retinoid X receptor. sod: Superoxide dismutase; trx: Thioredoxin; gpx: Glutathione peroxidase; ho: Heme oxygenase.