Probing the Cell Apoptosis Pathway Induced by Perfluorooctanoic Acid and Perfluorooctane Sulfonate at the Subcellular and Molecular Levels.

Abstract

As typical perfluorinated compounds (PFCs), perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have been detected in various environmental media and their toxic effects have been extensively studied. Nevertheless, it remains unclear how PFCs cause cell apoptosis in healthy hepatocytes by inducing oxidative stress at the subcellular and molecular levels. In this study, the apoptotic pathways induced by PFOA and PFOS were explored. Besides, the effects of PFCs on the structure and function of lysozyme (LYZ) were investigated. After PFOA and PFOS exposure, the cell membrane and mitochondrial membrane potential were damaged. Further, PFOA and PFOS increased intracellular Ca2+ levels to 174.41 ± 1.70 and 158.91 ± 5.94%, respectively. Ultimately, caspase-3 was activated, causing cell apoptosis. As an indirect antioxidant enzyme, the molecular structure of LYZ was destroyed after interacting with PFOA and PFOS. Both PFOA and PFOS bound to the active center of LYZ, leading to the decrease of LYZ activity to 91.26 ± 0.78 and 76.01 ± 4.86%, respectively. This study demonstrates that PFOA and PFOS inhibit LYZ function, which can reduce the body's ability to resist oxidative stress, and then lead to mitochondria-mediated apoptosis.