Dual function of peroxiredoxin I in lipopolysaccharide-induced osteoblast apoptosis via reactive oxygen species and the apoptosis signal-regulating kinase 1 signaling pathway

Lipopolysaccharide (LPS)-induced osteoblast Apoptosis is a prominent factor to the defect in periodontal tissue repair in periodontal disease. LPS challenge contributes to the production of Reactive Oxygen Species (ROS) in periodontitis, and peroxiredoxin 1 (Prx1) is an antioxidant protein that protect cells against oxidative damage from ROS. Without LPS stimulation, apoptotic rates were higher in both Prx1 knockout (Prx1^KO) and Prx1 overexpression (Prx1^OE) cells compared with wild type. After LPS stimulation, intracellular ROS in Prx1^KO cells showed the highest level and Prx1^OE cells showed the least. Treatment with LPS significantly elevated the expression of Bax, Cyto-c, and Caspase 3 in Prx1^KO cells compared with wild type, although this could be completely abolished by NAC. In Prx1^OE cells, the expression and activation of ASK1 were significantly increased, and this was slightly reduced by LPS stimulation. NQDI-1 completely abolished the increased phosphorylation of JNK and p38 and the expression of Caspase 3 in LPS-stimulated cells. These results indicate that Prx1 eliminates intracellular ROS and exhibits a cytoprotective role in LPS-induced Apoptosis. However, under physiological conditions, Prx1 overexpression acts as a H₂O₂ messenger, triggering the expression of ASK1 and its downstream cascades.