Zinc ferrite nanoparticles activate IL-1b, NFKB1, CCL21 and NOS2 signaling to induce mitochondrial dependent intrinsic apoptotic pathway in WISH cells

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• 作者：Quaiser Saquib ; Abdulaziz A. Al-Khedhairy ; Javed Ahmad ; Maqsood A. Siddiqui ; Sourabh Dwivedi ; Shams T. Khan ; Javed Musarrat
• 关键词：Zinc ferrite ; Oxidative stress ; DNA damage ; Nanoparticles ; Apoptosis ; Cytotoxicity
• 刊名：Toxicology and Applied Pharmacology
• 出版年：1 December, 2013
• 年：2013
• 卷：273
• 期：2
• 页码：289-297
• 全文大小：1380 K

文摘

The present study has demonstrated the translocation of zinc ferrite nanoparticles (ZnFe₂O₄-NPs) into the cytoplasm of human amnion epithelial (WISH) cells, and the ensuing cytotoxicity and genetic damage. The results suggested that in situ NPs induced oxidative stress, alterations in cellular membrane and DNA strand breaks. The [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) and neutral red uptake (NRU) cytotoxicity assays indicated 64.48 卤 1.6% and 50.73 卤 2.1% reduction in cell viability with 100 渭g/ml of ZnFe₂O₄-NPs exposure. The treated WISH cells exhibited 1.2-fold higher ROS level with 0.9-fold decline in membrane potential (螖唯m) and 7.4-fold higher DNA damage after 48 h of ZnFe₂O₄-NPs treatment. Real-time PCR (qPCR) analysis of p53, CASP 3 (caspase-3), and bax genes revealed 5.3, 1.6, and 14.9-fold upregulation, and 0.18-fold down regulation of bcl 2 gene vis-脿-vis untreated control. RT² Profiler鈩?PCR array data elucidated differential up-regulation of mRNA transcripts of IL-1b, NFKB1, NOS2 and CCL21 genes in the range of 1.5 to 3.7-folds. The flow cytometry based cell cycle analysis suggested the transfer of 15.2 卤 2.1% (p < 0.01) population of ZnFe₂O₄-NPs (100 渭g/ml) treated cells into apoptotic phase through intrinsic pathway. Over all, the data revealed the potential of ZnFe₂O₄-NPs to induce cellular and genetic toxicity in cells of placental origin. Thus, the significant ROS production, reduction in 螖唯m, DNA damage, and activation of genes linked to inflammation, oxidative stress, proliferation, DNA damage and repair could serve as the predictive toxicity and stress markers for ecotoxicological assessment of ZnFe₂O₄-NPs induced cellular and genetic damage.