Perfluorooctane sulfonate causes HK-2 cell injury through ferroptosis and endoplasmic reticulum stress pathways.

Abstract

Perfluorooctane sulfonate (PFOS) is a synthetic persistent organic compound that is widely used in industrial products. Studies have shown that PFOS can accumulate in environment and pose a threat to human health. As the kidney is the main excretory organ for PFOS, it is important to study PFOS damage to the kidney to investigate its toxicity. Human proximal tubular epithelial cells (HK-2) were treated with 200 μM PFOS or 1 μM Fer-1. Cell viability, the levels of MDA, GSH, intracellular iron ion, and GPX-4 were determined. The expression of KIM-1 and endoplasmic reticulum stress (ERS) related proteins were determined. The expression levels of KIM-1, a marker of renal tubular injury, and ERS-related proteins, GRP78, ATF6, IRE1, and PERK, were significantly increased in HK-2 cells exposed to PFOS. The levels of MDA and intracellular total iron ion also were significantly increased in HK-2 cells exposed to PFOS and the levels of GSH and GPX-4 were significantly decreased. PFOS can damage HK-2 cells through ferroptosis and endoplasmic reticulum stress, which provides a theoretical foundation for exploring the toxicity of PFOS to the kidney.