Background
Previous studies suggested that the nuclear receptor peroxisome proliferator-activated receptor (PPAR)-δ plays an essential role in cellular responses against oxidative stress.
Conclusion
The gene encoding catalase is a target of PPAR-δ, and this novel catalase-mediated pathway plays a critical role in the cellular response elicited by PPAR-δ against oxidative stress.
Methods
The present study was undertaken in HDFs by performing real-time polymerase chain reaction, gene silencing, cytotoxicity and reporter gene assay, analyses for catalase and reactive oxygen species, and immunoblot analyses.
Objective
To investigate how PPAR-δ elicits cellular responses against oxidative stress in primary human dermal fibroblasts (HDFs) exposed to ultraviolet B (UVB).
Results
The PPAR-δ activator GW501516 upregulated expression of catalase and this upregulation was attenuated by PPAR-δ-targeting siRNA. GW501516-activated PPAR-δ induced catalase promoter activity through a direct repeat 1 response element. Mutation of this response element completely abrogated transcriptional activation, indicating that this site is a novel type of PPAR-δ response element. In addition, GW501516-activated PPAR-δ counteracted the reductions in activity and expression of catalase induced by UVB irradiation. These recovery effects were significantly attenuated in the presence of PPAR-δ-targeting siRNA or the specific PPAR-δ antagonist GSK0660. GW501516-activated PPAR-δ also protected HDFs from cellular damage triggered by UVB irradiation, and this PPAR-δ-mediated reduction of cellular damage was reversed by the catalase inhibitor or catalase-targeting siRNA. These effects of catalase blockade were positively correlated with accumulation of reactive oxygen species in HDFs exposed to UVB. Furthermore, GW501516-activated PPAR-δ targeted peroxisomal hydrogen peroxide through catalase in UVB-irradiated HDFs.