Oxidative Stress in Cardiovascular Diseases and Obesity: Role of p66Shc and Protein Kinase C

Figure 1

(a) Signal transduction pathway of p66^Shc in oxidative condition. Oxidative stress induces PKCβ activation and p66^Shc phosphorylation allowing its recognition by Pin-1 and the transfer from the cytosol to the mitochondrion, where it induces PTP opening. In the nucleus, p66^Shc  inhibits the FOXO transcription factors, causing a decrease of antioxidant enzymes level, while at the plasma membrane p66^Shc promotes ROS production by rac1 and NADPH oxidase activation. (b) Focusing on loop between PKCβ,  p66^Shc, and H₂O₂. PKCβ activation by H₂O₂ promotes p66^Shc phosphorylation. Active p66^Shc induces H₂O₂ production, which in addition to H₂O₂ present endogenously leads to PKCβ activation.