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Mild Hypothermia Prevents NO-Induced Cytotoxicity in Human Neuroblastoma Cells Via Induction of COX-2

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Abstract

The cold-inducible protein RBM3 mediates hypothermic neuroprotection against nitric oxide (NO)-induced cell death. Meanwhile, it is well-known that cyclooxygenase-2 (COX-2) is upregulated by RBM3 in several types of cells; however, it is still unclear whether COX-2 contributes to the neuroprotective effects of mild hypothermia/RBM3 against NO-induced cell death. Using human SH-SY5Y neuroblastoma cells, it was revealed that NO remarkably downregulates the expression of COX-2 at both mRNA and protein levels. When COX-2 was silenced using siRNA technique, cells became more sensitive to NO-induced cell death. Conversely, the overexpression of COX-2 significantly prevented NO-induced cell death in SH-SY5Y cells, indicating a pro-survival role of COX-2. Upon mild hypothermia pre-treatment, COX-2 was notably induced at both mRNA and protein levels; however, COX-2 silencing abrogated hypothermia-related neuroprotection against NO-induced cell death. Furthermore, it was revealed that either silencing or overexpression of RBM3 had no effects on the expression of COX-2 in SH-SY5Y cells. These findings suggest that mild hypothermia could protect neuroblastoma cells against NO-induced cell death by inducing COX-2 in a RBM3-independent manner.

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Acknowledgements

We thank Medsci (www.medsci.com) for the linguistic assistance during the preparation of this manuscript.

Funding

This work was sponsored for HY by National Natural Science Foundation of China (81771336 and U1704186), Henan Program for Science and Technology Development (162102310490), and Henan Key Laboratory of Biological Psychiatry (ZDSYS2015005).

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  1. Bing-Bing Lei and Fei Ju contributed equally to this work.

Authors and Affiliations

  1. School of Life Science and Technology, Xinxiang Medical University, Xinxiang, 453003, China

    Bing-Bing Lei, Qi-Ran Fu, Xin Yuan, Wen-Xin Song, Guo-Qin Ji, Lei Wang, Bin-Feng Cheng, Mian Wang & Hai-Jie Yang

  2. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, 453003, China

    Fei Ju & Mian Wang

  3. Beijing Genomics Institute-Shenzhen, Shenzhen, 518083, China

    Kai-Yu Lei

  4. Henan Key Lab of Biological Psychiatry, Second Affiliated Hospital of Xinxiang Medical University, 601 Jinsui Road, Xinxiang, 453003, Henan, China

    Hai-Jie Yang

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  1. Bing-Bing Lei
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Lei, BB., Ju, F., Fu, QR. et al. Mild Hypothermia Prevents NO-Induced Cytotoxicity in Human Neuroblastoma Cells Via Induction of COX-2. J Mol Neurosci 67, 173–180 (2019). https://doi.org/10.1007/s12031-018-1222-z

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