Peroxiredoxin Ⅱ silencing aggravates FA-induced myelotoxicity through triggering PI3K pathway mediated by PTEN.

Formaldehyde (FA) is a critical industrial compound implicated in leukemogenesis via the induction of oxidative stress. Our previous studies observed aberrant expression of peroxiredoxin II (PrxII), phosphatase and tensin homologue (PTEN), phosphoinositide 3-kinase (PI3K), and protein kinase B (Akt) in FA-exposed bone marrow cells (BMCs) under conditions of oxidative stress. We speculate that the PrxII gene may be functionally linked to the PI3K pathway in formaldehyde-induced oxidative damage. Therefore, in the current study, we first used a specific PI3K inhibitor (LY294002, 10 μM) to suppress the PI3K pathway at 100 μM FA, and co-treated mouse bone marrow cells for 24 hours to investigate their potential interactions. We then evaluated the expression levels of PrxII, PTEN, PI3K, and Akt (via qRT-PCR and Western blot analysis), as well as the BMC's viability (CCK-8 assay), ROS levels (DCFH-DA), and cell apoptosis (Annexin V/PI staining). Additionally, to explore the potential regulatory role of PrxⅡ in the PI3K pathway, we employed siRNA-mediated PrxⅡ gene silencing through a small interfering RNA and subsequently measured PTEN, PI3K, and Akt mRNA and protein levels using qRT-PCR and Western blot analysis. We observed that inhibition of the PI3K pathway with 10 μM LY294002 mitigated FA-induced oxidative damage in BMCs, as evidenced by improved cell viability, reduced ROS levels, and decreased apoptosis rates. Moreover, PrxII silencing led to downregulation of PTEN expression while concurrently activating the PI3K/Akt signaling cascade. This study provides evidence that PrxII silencing may trigger the PI3K pathway mediated by PTEN gene, thereby exacerbating FA-induced oxidative injury.