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 1,000 µM 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.

Peroxidase expression is decreased by palmitate in cultured podocytes but increased in podocytes of advanced diabetic nephropathy

“…Although we found no change in podocyte catalase expression by H 2 O 2 , others noted it either decreased (Y.‐H. Chen, Lin, Liu, & Su, ) or increased (Lu et al, ). Interestingly, patients with catalase gene mutation have life‐long increased H 2 O 2 concentration, which has cytotoxic effects on pancreatic cells, to be a risk factor for diabetes (Goth, ).…”

A review of the role of cav-1 in neuropathology and neural recovery after ischemic stroke

“…And mitochondrial dysfunction is considered as a hallmark of intrinsic apoptosis. In E11 podocytes, cav-1 OE attenuated H 2 O 2 -induced oxidative stress responses and preserved mitochondrial function, as well as significantly suppressing apoptosis [153]. Moreover, various cav-1-deficient cells have displayed mitochondrial dysfunction including impaired energy generation, and increased mitochondrial ROS production [154–156].…”

The importance of caveolins and caveolae to dermatology: Lessons from the caves and beyond

“…In addition to previously mentioned functions, several studies have found that Cav1 may also be related to stress-induced premature senescence in a biphasic manner. Initially, it appeared that Cav1 can be induced by sub-cytotoxic levels of H 2 O 2 , to accelerate premature senescence and mitochondrial dysfunction [182][183][184][185] ; however, when Cav1 expression is inhibited either in Cav1-null mice, or by using antisense Cav1, premature senescence by H 2 O 2 does not occur. [182,186] Recently, it has also been shown that strong suppression of Cav1 induces premature senescence in a p53-p21-dependent manner.…”