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

Abstract

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 1,000µM H2O2 for 1h 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 48h. 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.