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Cold-Inducible Protein RBM3 Protects UV Irradiation-Induced Apoptosis in Neuroblastoma Cells by Affecting p38 and JNK Pathways and Bcl2 Family Proteins

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Abstract

Induced by hypothermia, cold-inducible protein RBM3 (RNA-binding protein motif 3), has been implicated in neuroprotection against various toxic insults such as hypoxia and ischemia. However, whether mild hypothermia and RBM3 prevent neural cells from UV irradiation-elicited apoptosis is unclear. In the present study, human neuroblastoma cell line SH-SY5Y was used as a cell model for neural cell death, and it was demonstrated that mild hypothermia protects SH-SY5Y cells from UV irradiation-induced apoptosis. However, the protective effect of mild hypothermia was abrogated when RBM3 was silenced. Conversely, the overexpression of RBM3 rescued SH-SY5Y cells from UV-induced apoptosis, as indicated by the decreased levels of cleaved caspase-3 and PARP, and increased cell survival. The analysis on the mechanism underlying RBM3-mediated neuroprotection against UV insult showed that RBM3 could substantially block the activation of p38 and JNK signaling pathways. In addition, the overexpression of RBM3 reduced the expression of pro-apoptotic proteins Bax and Bad, leaving the pro-survival protein Bcl-2 unaffected. In conclusion, RBM3 is the key mediator of mild hypothermia-related protection against UV in neuroblastoma cells, and the neuroprotective effect might be exerted through interfering with pro-apoptotic signaling pathways p38 and JNK and regulating pro-apoptotic proteins Bax and Bad.

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Acknowledgements

We thank LetPub (www.letpub.com) for the linguistic assistance during the preparation of this manuscript. This work was sponsored by National Natural Science Foundation of China (81771336), Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine (XTCX-2015-ZD3), Disciplinary group of Psychology and Neuroscience of Xinxiang Medical University, Henan Key Laboratory of Biological Psychiatry (ZDSYS2015005), Graduate Scientific Research Innovation Support Project of Xinxiang Medical University (YJSCX201649Y), Henan Program for Science and Technology Development (162102310490), and Henan Educational Committee Program for Science and Technology Development of Universities (16A180015).

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Authors and Affiliations

  1. School of Life Science and Technology, Xinxiang Medical University, 601 Jinsui Road, Xinxiang, Henan, 453003, China

    Rui-Juan Zhuang, Jian Ma, Xiang Shi, Fei Ju, Shuang-Ping Ma, Lei Wang, Bin-Feng Cheng, Mian Wang, Tong Li, Zhi-Wei Feng & Hai-Jie Yang

  2. Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang, 453003, China

    Rui-Juan Zhuang, Mian Wang, Zhi-Wei Feng & Hai-Jie Yang

  3. Henan Key Lab of Biological Psychiatry, Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453003, China

    Rui-Juan Zhuang & Hai-Jie Yang

  4. Department of Anesthesia, Second People Hospital of Xinxiang, Xinxiang, 453003, China

    Yan-Wen Ma

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  1. Rui-Juan Zhuang
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Fig. S1

UV irradiation induces cytotoxicity in SH-SY5Y neuroblastoma cells. Cells were treated UV irradiation at various doses and cell viability was assessed by MTT assay. ***p < 0.001 versus control group. All results shown are representative of three independent experiments. (GIF 18 kb)

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Zhuang, RJ., Ma, J., Shi, X. et al. Cold-Inducible Protein RBM3 Protects UV Irradiation-Induced Apoptosis in Neuroblastoma Cells by Affecting p38 and JNK Pathways and Bcl2 Family Proteins. J Mol Neurosci 63, 142–151 (2017). https://doi.org/10.1007/s12031-017-0964-3

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