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Inhibition of NF-κB activity by aminoguanidine alleviates neuroinflammation induced by hyperglycemia

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Abstract

Neuroinflammation is a key feature of cerebral complication which is associated with diabetes mellitus (DM). Inducible nitric oxide synthase (iNOS) is implicated in the pathogenesis of neuroinflammation. However, how iNOS facilitates the development of inflammation in brain is still unidentified. The aim of the present study was to investigate the association of iNOS and neuroinflammation in diabetic mice, and elucidate the potential mechanisms underlying aminoguanidine (AG), the selective inhibitor of iNOS, protected neurons against inflammation in diabetic mice. In present experiment, diabetic mice model were established by a single intraperitoneal injection of streptozotocin (STZ). AG was administered to diabetic mice for ten weeks after this disease induction. Then we measured iNOS activity in the serum and brain, detected the glial fibrillary acidic protein (GFAP) and ionised calcium binding adaptor molecule-1 (Iba-1) expressions in the brain. Moreover, nuclear factor-kappa B (NF-κB) in cytoplasm and nucleus were tested by IP and WB. Results revealed that high expression of iNOS in serum and brain could be reversed by AG treatment. Furthermore, AG could also inhibit GFAP and Iba-1 expressions, and NF-κB nuclear translocation by inhibiting it from binding to iNOS in cytoplasm. Our findings indicated that iNOS can combine with NF-κB in cytoplasm and promote its nuclear transfer in diabetic mice. Furthermore, AG decreased neuroinflammation through inhibiting iNOS activity and reducing NF-κB nuclear translocation by promoting its dissociation with iNOS in cytoplasm.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81371300, 81501042, 81671208), Natural Science Foundation of Jiangsu Province (BK20150218), Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) and the Qing Lan Project of Jiangsu Province. The experiments in this article were completed in Research Facility Center for Morphology, and thanks the teachers Hongyan Dong, Ting Li, Honghua Yuan, Hongli Yu, Fuxing Dong, Zhiwei Liu, Qingli Huang and Meng Wang for their support and help during the experiments.

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  1. Yuanjian Song, Fang Zhang and Changjiang Ying contributed equally to this work.

Authors and Affiliations

  1. Department of Genetics, Research Facility Center for Morphology, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China

    Yuanjian Song & Fang Zhang

  2. Department of Endocrinology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221002, People’s Republic of China

    Changjiang Ying

  3. Department of Clinical Medicine, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China

    Kiran Ashok Kumar

  4. Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China

    Xiaoyan Zhou

  5. Laboratory of Morphology, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, People’s Republic of China

    Xiaoyan Zhou

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  1. Yuanjian Song
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Correspondence to Xiaoyan Zhou.

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Song, Y., Zhang, F., Ying, C. et al. Inhibition of NF-κB activity by aminoguanidine alleviates neuroinflammation induced by hyperglycemia. Metab Brain Dis 32, 1627–1637 (2017). https://doi.org/10.1007/s11011-017-0013-5

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