Palmitate enhanced the cytotoxicity of ZnO nanomaterials possibly by promoting endoplasmic reticulum stress.
We recently synthesized ZnO nanomaterials (denoted as ZnO nanorods [NRs] and Mini-NRs) and suggested that their cytotoxicity could be related with the activation of endoplasmic reticulum (ER) stress apoptosis. However, in a complex biological microenvironment, the ER stress-apoptosis pathway could also be modulated by biological molecules, such as free fatty acids, leading to unpredicted biological effects. In this study, we investigated the combined toxicity of ZnO NRs/Mini-NRs and palmitate (PA) to THP-1 macrophages. PA influenced the zeta potential and solubility of ZnO NRs and ZnO Mini-NRs in water, which indicated a change of colloidal stability. Exposure to ZnO NRs and Mini-NRs dose-dependent decreased cellular viability and release of soluble monocyte chemotactic protein 1 (sMCP-1), and these effects were significantly promoted with the presence of PA. However, ZnO NR- and Mini-NR-induced intracellular Zn ions or reactive oxygen species were not significantly affected by PA. ZnO NRs and ZnO Mini-NRs significantly promoted the expression of ER stress genes HSPA5, DDIT3, XBP-1s and apoptotic gene CASP3, whereas PA also modestly promoted the expression of HSPA5, DDIT3 and CASP3. Interestingly, the ER stress inducer thapsigargin showed a similar effect as PA to promote the cytotoxicity of ZnO NRs and ZnO Mini-NRs. It is suggested that PA might promote the cytotoxicity of ZnO NRs and ZnO Mini-NRs possibly by promoting ER stress.
['Chen|Jiamao|J|', 'Yang|Ting|T|', 'Long|Jimin|J|', 'Ding|Yanhuai|Y|', 'Li|Juan|J|', 'Li|Xianqiang|X|', 'Cao|Yi|Y|0000-0002-9282-0051']
D002470:Cell Survival D004305:Dose-Response Relationship, Drug D004357:Drug Synergism D000091342:Endoplasmic Reticulum Chaperone BiP D059865:Endoplasmic Reticulum Stress D006801:Humans D009000:Monocytes D053758:Nanoparticles D010168:Palmitates D017382:Reactive Oxygen Species D013499:Surface Properties D000074084:THP-1 Cells D015034:Zinc Oxide
palmitate cytotoxicity ZnO nanomaterials endoplasmic reticulum (ER) stress THP-1 macrophages