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Neuroprotective Effect of CeO2@PAA-LXW7 Against H2O2-Induced Cytotoxicity in NGF-Differentiated PC12 Cells

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Abstract

CeO2 nanoparticles (nanoceria) have been used in many studies as a powerful free radical scavenger, and LXW7, a small-molecule peptide, can specifically target the integrin αvβ3, whose neuroprotective effects have also been demonstrated. The objective of this study is to observe the neuroprotective effect and potential mechanism of CeO2@PAA-LXW7, a new compound that couples CeO2@PAA (nanoceria modified with the functional group of polyacrylic acid) with LXW7 via a series of chemical reactions, in H2O2-induced NGF-differentiated PC12 cells. We examined the effects of LXW7, CeO2@PAA, and CeO2@PAA-LXW7 on the viability of primary hippocampal neurons and found that there was no significant difference under control conditions, but increased cellular viability was observed in the case of H2O2-induced injury. We used H2O2-induced NGF-differentiated PC12 cells as the classical injury model to investigate the neuroprotective effect of CeO2@PAA-LXW7. In this study, LXW7, CeO2@PAA, and CeO2@PAA-LXW7 inhibit H2O2-induced oxidative stress by reducing the production of reactive oxygen species (ROS) and regulating Bax/Bcl-2, cleaved caspase-3 and mitochondrial cytochrome C (cyto C) in the apoptotic signaling pathways. We found that the levels of phosphorylation of focal adhesion kinase (FAK) and of signal transducer and activator of transcription 3 (STAT3) increased significantly in H2O2-induced NGF-differentiated PC12 cells, whereas LXW7, CeO2@PAA, and CeO2@PAA-LXW7 suppressed the increase to different degrees. Among the abovementioned changes, the inhibitory effect of CeO2@PAA-LXW7 on H2O2-induced changes, including the increases in the levels of p-FAK and p-STAT3, is more obvious than that of LXW7 or CeO2@PAA alone. In summary, these results suggest that integrin signaling participates in the regulation of apoptosis via the regulation of ROS and of the apoptosis pathway in H2O2-induced NGF-differentiated PC12 cells. LXW7, CeO2@PAA, and CeO2@PAA-LXW7 can play neuroprotective roles by counteracting the oxidative stress and apoptosis induced by H2O2 in NGF-differentiated PC12 cells. CeO2@PAA-LXW7 exerting a more powerful synergistic effect via the conjunction of LXW7 and CeO2@PAA.

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Acknowledgements

This study was funded by Health and Family Planning Commission of Shenzhen Municipality Fund (No. 201401027). The drug synthetic process was supported by the Inner Mongolia University Startup Fund Project (21300-5145152), the Inner Mongolia Education Department Key Project (NJZZ16015), and the Inner Mongolia Natural Science Foundation (2016MS0216).

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Authors and Affiliations

  1. Department of Neurology, Peking University Shenzhen Hospital, Shenzhen, 518036, Guangdong, China

    Jingjing Jia, Jieshan Chi, Xiaoma Liu, Jingjing Sun, Qizhi Xie, Sijia Peng & Li Yi

  2. Department of Phoenix international medical center, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China

    Ting Zhang

  3. College of Chemistry and Chemical Engineering, Inner Mongolia University, Hohhot, Inner Mongolia, China

    Changyan Li

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  1. Jingjing Jia
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  4. Xiaoma Liu
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Correspondence to Changyan Li or Li Yi.

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Jia, J., Zhang, T., Chi, J. et al. Neuroprotective Effect of CeO2@PAA-LXW7 Against H2O2-Induced Cytotoxicity in NGF-Differentiated PC12 Cells. Neurochem Res 43, 1439–1453 (2018). https://doi.org/10.1007/s11064-018-2559-y

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