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  • Title: Palmitate enhanced the cytotoxicity of ZnO nanomaterials possibly by promoting endoplasmic reticulum stress.
    Author: Chen J, Yang T, Long J, Ding Y, Li J, Li X, Cao Y.
    Journal: J Appl Toxicol; 2019 May; 39(5):798-806. PubMed ID: 30620997.
    Abstract:
    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.
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