Involvement of PINK1/parkin-mediated mitophagy in ZnO nanoparticle-induced toxicity in BV-2 cells.
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, aPINK1gene 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 andPINK1-/-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 thePINK1gene 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.
Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China; Department of Pediatric Dentistry, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, People's Republic of China.
Limin
L
Wei
Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China; Department of Pediatric Dentistry, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, People's Republic of China.
Jianfeng
J
Wang
Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
Aijie
A
Chen
Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
Jia
J
Liu
Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
Xiaoli
X
Feng
Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
Longquan
L
Shao
D000818:Animals; D001343:Autophagy / Q000187:drug effects; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D063306:Mitophagy / Q000187:drug effects*; D053758:Nanoparticles / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D011494:Protein Kinases / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014162:Transfection; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D015034:Zinc Oxide / Q000494:pharmacology / Q000633:toxicity*; D000099202:PTEN-Induced Putative Kinase
D011494:Protein Kinases; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D044767:Ubiquitin-Protein Ligases; D015034:Zinc Oxide; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein
PINK1/parkin; autophagy; mitophagy; zinc oxide nanoparticles neurotoxicity