Peroxiredoxin1 Regulates ASK1 and p38 Expression in Oxidative Stress-related Oral Leukoplakia

Objectives: The aim of this study was to investigate the expression of peroxiredoxin1(Prx1) and its relationship with apoptosis signal-regulating Kinase 1(ASK1) and p38 in oral leukoplakia (OLK) tissues and human oral precancerous DOK cells treated with H₂O₂ .
Methods: Samples of 20 OLK and 10 normal oral mucosa were used to study the relationship of peroxiredoxin1(Prx1) and apoptosis signal-regulating Kinase 1(ASK1) and p38 . The expression of Prx1, ASK1 and p38 mRNA and protein was detected by Quantitative Real-Time PCR and Western Blot analysis, respectively. Flow cytometry was used to detect the cell apoptosis. The interaction between Prx1 and ASK1 was examined in H₂O₂ treated DOK cells both in vivo by co-immunoprecipitation as well as in vitro through GST pull-down assays.
Results: Compared with normal oral mucosa, the levels of Prx1, ASK1 and p38 mRNA elevated (P＜0.05), and the protein expression of Prx1, phosphorylated-ASK1(p-ASK1) and phosphorylated-p38（p-p38）were significantly higher in the OLK tissues (P＜0.05). In Prx1-knockdown DOK cells, ASK1 and p38 were activated, leading to more apoptosis in response to H₂O₂. No obvious interaction between Prx1 and ASK1 was detected in DOK cells treated with H₂O₂.
Conclusions: Prx1 appears to be involved in OLK pathogenesis. It may participate in providing resistance against extracellular damages from oxidative stress via inhibition of ASK1-induced p38MAPK apoptotic signal pathway. Targeting Prx1 might offer a new strategy for the treatment of OLK patients.