LAMP-2 mediates oxidative stress-dependent cell death in Zn2+-treated lung epithelium cells

Abstract

Zinc is an essential element for the biological system. However, excessive exogenous Zn2+ would disrupt cellular Zn2+ homeostasis and cause toxicity. In particular, Zinc salts or ZnO nanoparticles exposure could induce respiratory injury. Although previous studies have indicated that organelle damage (including mitochondria or lysosomes) and reactive oxygen species (ROS) production are involved in Zn2+-induced toxicity, the interplay between mitochondria/lysosomes damage and ROS production is obscure. Herein, we demonstrated that Zn2+ could induce deglycosylation of lysosome-associated membrane protein 1 and 2 (LAMP-1 and LAMP-2), which primarily locate in late endosomes/lysosomes, in A549 lung epithelium cells. Intriguingly, LAMP-2 knockdown further aggravated Zn2+-mediated ROS production and cell death, indicating LAMP-2 (not LAMP-1) was involved in Zn2+-induced toxicity. Our results provide a new insight that LAMP-2 contributes to the ROS clearance and cell death induced by Zn2+ treatment, which would help us to get a better understanding of Zn2+-induced toxicity in respiratory system.