Qin Xia, Zhang Jun, Wang Bin, Xu Ge, Zou Zhen
Institute of Life Sciences, Chongqing Medical University, 400016 Chongqing, China; Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, 400016 Chongqing, China.
Institute of Life Sciences, Chongqing Medical University, 400016 Chongqing, China.
Biochem Biophys Res Commun. 2017 Jun 17;488(1):177-181. doi: 10.1016/j.bbrc.2017.05.030. Epub 2017 May 5.
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.
锌是生物系统中的必需元素。然而，过量的外源性锌会破坏细胞内锌稳态并导致毒性。特别是，接触锌盐或氧化锌纳米颗粒会诱发呼吸道损伤。尽管先前的研究表明细胞器损伤（包括线粒体或溶酶体）和活性氧（ROS）生成与锌诱导的毒性有关，但线粒体/溶酶体损伤与ROS生成之间的相互作用尚不清楚。在此，我们证明锌可诱导A549肺上皮细胞中主要位于晚期内体/溶酶体的溶酶体相关膜蛋白1和2（LAMP-1和LAMP-2）去糖基化。有趣的是，LAMP-2基因敲低进一步加剧了锌介导的ROS生成和细胞死亡，表明LAMP-2（而非LAMP-1）参与了锌诱导的毒性作用。我们的研究结果提供了一个新的见解，即LAMP-2有助于锌处理诱导的ROS清除和细胞死亡，这将有助于我们更好地理解锌在呼吸系统中诱导的毒性。
