Paraquat induces apoptosis, programmed necrosis, and immune dysfunction in CIK cells via the PTEN/PI3K/AKT axis

Paraquat (PQ) is a highly water-soluble, non-selective herbicide. Due to water pollution and lack of specific medicines, it is extremely harmful to humans and aquatic animals. Oxidative stress and apoptosis can affect the immune function of the body. However, the effects and mechanisms of PQ on the immune function, apoptosis and programmed necrosis on CIK cells are still unclear. Therefore, we constructed low (L, 50 mu mol/L), medium (M, 100 mu mol/L), and high (H, 150 mu mol/L) dose models of PQ exposure on CIK cells. The expression of oxidative stress-related indexes (MDA, CAT, GSH-Px and SOD) and interrelated genes were examined by flow cytometry, qRT-PCR, and western blotting methods. Our data demonstrated that PQ treatment caused an increase in MDA content and the decreases in the activities of antioxidase and antioxidants (SOD, GSH-Px and CAT) on CIK cells (p < 0.05). We also discovered the PTEN/PI3K/AKT pathway was significantly activated in a dose dependent manner (p < 0.05). Furthermore, the proportion of programmed necrosis cells increased dramatically at PQ doses from 0 mu mol/L to 150 mu mol/L. Apoptosis and necrosis-related genes also showed dose-dependent changes (p < 0.05). Briefly, PQ exposure leads to apoptosis and programmed necrosis via the oxidative stress and PTEN/PI3K/ AKT pathway, thereby causing immune dysfunction of CIK cells. This study enriches the toxic influences of PQ on the cells of aquatic organisms and provides a reference for comparative medicine.

Automated summary

Exposure to paraquat leads to oxidative stress and activation of the PTEN/PI3K/AKT pathway, resulting in apoptosis and programmed necrosis in CIK cells, leading to immune dysfunction.