Iron Oxide Nanoparticles Induces Cell Cycle-Dependent Neuronal Apoptosis in Mice
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Iron oxide (Fe2O3) nanoparticles (NPs) with its unique magnetic and paramagnetic properties are popular in biomedical applications. Some of their neurotoxic mechanisms due to repeated administration are proven. However, we speculate that the neuronal damage might be due to apoptosis resulting from unusual cell cycle entry. Moreover, iron accumulation has been shown to be closely associated with most of the neurodegenerative disorders. Thus, in the current study, mice were orally (po) treated with the Fe2O3-NPs to investigate cell cycle-associated events/components and occurrence of apoptosis. A subsequent increase in oxidant levels was observed with the iron accumulation due to Fe2O3-NPs exposure. The accumulated β-amyloid and reduced level of cdk5 seem to aid in the cell cycle entry and forcing progression towards apoptosis. Expression of Cyclin D1 and pRb (Ser 795) indicate the cell cycle re-entry of neurons. Overexpression of RNA Pol II and PARP cleavage suggests DNA damage due to Fe2O3-NPs exposure. Further, hyperphosphorylation of p38 (Thr 180/Tyr 182) confirms the activation of DNA damage-dependent checkpoint. Expression patterns of pro- and anti-apoptotic markers, TUNEL and TEM indicate the occurrences of apoptosis.
KeywordsIron oxide NPs Cell cycle Apoptosis β-amyloid Oxidative stress
The authors would like to acknowledge Sophisticated Analytical Instrument Facility, All India Institute of Medical science (AIIMS), New Delhi, for the technical assistance in transmission electron microscopy. Vijayprakash Manickam acknowledges the UGC-BSR fellowship (UGC-BSR-No.F.7-25/2007) funded by UGC-BSR, New Delhi, India. We also thank the UGC-SAP DRS II (F-3-30/2013) and DST FIST (SR/FST/LSI-618/2014), New Delhi, India, for their partial financial assistance.
Compliance with Ethical Standards
All the experiments were conducted in accordance with the ethical norms approved by Institutional Animal Ethical Committee (722/02/A/CPCSEA).
Conflict of Interest
The authors declare that they have no conflict of interest.
All procedures performed in this study involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.
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