Figures & data
Figure 1. Role of p66Shc in regulation of ROS and apoptosis. Phosphorylated p66Shc (p-p66Shc) stimulates NADPH oxidase complex formation and ROS generation. In addition, p66Shc reduces the expression of antioxidant enzymes (e.g., MnSOD), p-p66Shc is transported into mitochondria, and then p66shc is released from the high -molecular-mass complex that contains TOM, TIM, and mHSP70, the released p66Shc acts as an oxidoreductase and promotes ROS generation, eventually leading to cellular oxidative injury and apoptosis. (see details in the text).
Figure 2. Role of p66Shc in renal tubular cells. Phosphorylated p66Shc(p-p66Shc) increases mitochondrially mediated oxidative stress in tubular epithelial cells, and promotes cellular apoptosis; thus ameliorating renal ischemia/reperfusion injury, tobacco-related kidney injury, and diabetic kidney disease; and also enhancing nephrotoxicity. In addition, p-p66Shc could aggravate renal ischemia/reperfusion injury and cisplatin-induced nephrotoxicity via diverse pathways as indicated in the figure. At times, p-p66Shc can also modulate cellular EMT and the expression of ECM. Overall, it appears that activation of p66Shc accelerates the progression of various kidney diseases (see details in the text).
Figure 3. Role of p66Shc in glomerular cells. In glomerular capillary lumen, p66Shc may act as a negative regulator of immune complexes and reduce the development of autoimmune glomerulonephritis. In addition, phosphorylated p66Shc regulates apoptosis of GMC and podocytes via different pathways in diabetic kidney disease, HIV-associated nephropathy and glomerulonephritis. Therefore, if signaling occurs at the level of mediation of downstream events by p66Shc, one would anticipate different outcomes in various glomerular disease processes (see details in the text). Note: Po, podocytes; Me, mesangial cells; Cap, capillary lumen; GN, glomerulonephritis; DKD, diabetic kidney disease; HIV-AN, HIV-associated nephropathy.
