H2O2 induces caveolin-1 degradation and impaired mitochondrial function in E11 podocytes

Increased intercellular reactive oxygen species (ROS) levels are the major cause of podocyte injury with proteinuria. Caveolin-1 (CAV-1) is an essential protein component of caveolae. CAV-1 participates in signal transduction and endocytic trafficking. Recent research has indicated that CAV-1 regulates oxidative stress-induced pathways. The present study used hydrogen peroxide (H2O2) at nontoxic concentrations to elevate the level of ROS in E11 podocytes. Treatment with 500 and 1,000 mu M H2O2 for 1 h significantly reduced CAV-1 expression levels. Simultaneously, the treatment significantly reduced the expression of the antioxidant enzymes glutamine-cysteine ligase catalytic subunit, superoxide dismutase 2 and catalase. To determine the role of CAV-1 in mediating oxidative stress, E11 podocytes were administered antenapedia-CAV-1 (AP-CAV-1) peptide for 48 h. The AP-CAV-1 treatment enhanced CAV-1 expression and inhibited cyclophilin A expression, thus reducing ROS-induced inflammation. Moreover, CAV-1 protected against H2O2-induced oxidative stress responses by enhancing the expression of antioxidant enzymes. Furthermore, CAV-1 attenuated H2O2-induced changes oxidative phosphorylation, and the expression of optic atrophy 1 and translocase of the inner membrane 23, as well as preserving mitochondrial function. CAV-1 treatment significantly suppressed apoptosis, as indicated by a higher B-cell lymphoma 2/BCL2-associated X protein ratio. Therefore, enhancing the expression of CAV-1 may be an important therapeutic consideration in treating podocyte injury.