International Journal of Nanomedicine (Mar 2017)
Involvement of PINK1/parkin-mediated mitophagy in ZnO nanoparticle-induced toxicity in BV-2 cells
Abstract
Limin Wei,1,2,* Jianfeng Wang,1,2,* Aijie Chen,1 Jia Liu,1 Xiaoli Feng,1 Longquan Shao1 1Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Pediatric Dentistry, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, People’s Republic of China *These authors contributed equally to this work Abstract: With the increasing application of zinc oxide nanoparticles (ZnO NPs) in biological materials, the neurotoxicity caused by these particles has raised serious concerns. However, the underlying molecular mechanisms of the toxic effect of ZnO NPs on brain cells remain unclear. Mitochondrial damage has been reported to be a factor in the toxicity of ZnO NPs. PINK1/parkin-mediated mitophagy is a newly emerging additional function of autophagy that selectively degrades impaired mitochondria. Here, a PINK1 gene knockdown BV-2 cell model was established to determine whether PINK1/parkin-mediated mitophagy was involved in ZnO NP-induced toxicity in BV-2 cells. The expression of total parkin, mito-parkin, cyto-parkin, and PINK1 both in wild type and PINK1-/- BV-2 cells was evaluated using Western blot analysis after the cells were exposed to 10 µg/mL of 50 nm ZnO NPs for 2, 4, 8, 12, and 24 h. The findings suggested that the downregulation of PINK1 resulted in a significant reduction in the survival rate after ZnO NP exposure compared with that of control cells. ZnO NPs were found to induce the transportation of parkin from the cytoplasm to the mitochondria, implying the involvement of mitophagy in ZnO NP-induced toxicity. The deletion of the PINK1 gene inhibited the recruitment of parkin to the mitochondria, causing failure of the cell to trigger mitophagy. The present study demonstrated that apart from autophagy, PINK1/parkin-mediated mitophagy plays a protective role in ZnO NP-induced cytotoxicity. Keywords: PINK1/parkin, mitophagy, autophagy, zinc oxide nanoparticles neurotoxicity
