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

Area of Science:

• Toxicology
• Molecular Biology
• Cell Biology

Background:

• Formaldehyde (FA) is linked to leukemia through oxidative stress.
• Aberrant expression of PrxII, PTEN, PI3K, and Akt occurs in FA-exposed bone marrow cells (BMCs).
• A potential functional link between PrxII and the PI3K pathway in FA-induced damage is hypothesized.

Purpose of the Study:

• To investigate the interaction between the PI3K pathway and PrxII in FA-induced oxidative damage.
• To elucidate the role of PrxII in regulating the PI3K/Akt signaling cascade.
• To assess the impact of PI3K inhibition and PrxII silencing on BMCs.

Main Methods:

• Quantitative real-time PCR (qRT-PCR) and Western blot analysis for gene and protein expression.
• Cell Counting Kit-8 (CCK-8) assay for cell viability.
• Detection of reactive oxygen species (ROS) using DCFH-DA.
• Apoptosis analysis via Annexin V/PI staining.
• siRNA-mediated PrxII gene silencing.

Main Results:

• Inhibition of the PI3K pathway with LY294002 reduced FA-induced oxidative damage, improving BMC viability and decreasing ROS and apoptosis.
• PrxII gene silencing resulted in PTEN downregulation and activation of the PI3K/Akt signaling pathway.
• These findings suggest PrxII silencing exacerbates FA-induced oxidative injury by activating the PI3K pathway via PTEN.

Conclusions:

• The PI3K pathway plays a protective role against formaldehyde-induced oxidative stress in BMCs.
• PrxII gene silencing activates the PI3K/Akt pathway, potentially mediated by PTEN, worsening FA-induced oxidative damage.
• PrxII emerges as a critical regulator in the context of formaldehyde-induced leukemogenesis and oxidative injury.