LAMP-2 mediates oxidative stress-dependent cell death in Zn-treated lung epithelium cells.

Zinc is an essential element for the biological system. However, excessive exogenous Zn would disrupt cellular Zn 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 Zn-induced toxicity, the interplay between mitochondria/lysosomes damage and ROS production is obscure. Herein, we demonstrated that Zn 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 Zn-mediated ROS production and cell death, indicating LAMP-2 (not LAMP-1) was involved in Zn-induced toxicity. Our results provide a new insight that LAMP-2 contributes to the ROS clearance and cell death induced by Zn treatment, which would help us to get a better understanding of Zn-induced toxicity in respiratory system.