1. Zinc ferrite nanoparticles activate IL-1b, NFKB1, CCL21 and NOS2 signaling to induce mitochondrial dependent intrinsic apoptotic pathway in WISH cells.
- Author
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Saquib, Quaiser, Al-Khedhairy, Abdulaziz A., Ahmad, Javed, Siddiqui, Maqsood A., Dwivedi, Sourabh, Khan, Shams T., and Musarrat, Javed
- Subjects
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NANOMEDICINE , *ZINC ferrites , *CHROMOSOMAL translocation , *EPITHELIAL cells , *CELL-mediated cytotoxicity , *DNA damage , *CELLULAR signal transduction , *NF-kappa B , *GENETIC toxicology , *DNA repair , *INTERLEUKIN-1 - Abstract
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±1.6% and 50.73±2.1% reduction in cell viability with 100μg/ml of ZnFe2O4-NPs exposure. The treated WISH cells exhibited 1.2-fold higher ROS level with 0.9-fold decline in membrane potential (ΔΨm) and 7.4-fold higher DNA damage after 48h 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-à-vis untreated control. RT2 Profiler™ 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±2.1% (p<0.01) population of ZnFe2O4-NPs (100μg/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 ΔΨm, 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. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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