Expression regulation of cold-inducible protein RBM3 by FAK/Src signaling for neuroprotection against rotenone under mild hypothermia

被引:7
作者
Yuan, Xin [1 ]
Zhang, Jun [1 ]
Ma, Ting-Ting [1 ]
Zhuang, Rui-Juan [1 ]
Lei, Bing-Bing [1 ]
Wang, Lei [1 ]
Cheng, Bin-Feng [1 ]
Wang, Mian [1 ]
Yang, Hai-Jie [1 ]
机构
[1] Xinxiang Med Univ, Sch Life Sci & Technol, Affiliated Hosp 2, Henan Key Lab Biol Psychiat, Xinxiang 453003, Henan, Peoples R China
基金
中国国家自然科学基金;
关键词
Mild hypothermia; RBM3; Gene expression control; Neuroprotection; FAK; Src; RNA-BINDING PROTEINS; INDUCED APOPTOSIS; THERAPEUTIC HYPOTHERMIA; NEUROBLASTOMA-CELLS; FAK; TRANSDUCTION; HIBERNATION; MECHANISMS; SURVIVAL; IMPROVE;
D O I
10.1016/j.bbrc.2020.11.105
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Mild hypothermia is a well-established technique for alleviating neurological injuries in clinical surgery. RNA-binding protein motif 3 (RBM3) has been identified as a crucial factor in mediating hypothermic neuroprotection, providing its induction as a promising strategy for mimicking therapeutic hypothermia. However, little is known about molecular control of RBM3 and signaling pathways affected by hypothermia. In the present study, human SH-SY5Y neuroblastoma cells were used as a neural cell model. Screening of signaling pathways showed that cold exposure led to inactivation of ERK and AMPK pathways, and activation of FAK and PLC gamma pathways, with activities of p38, JNK and AKT pathways moderately changed. Next, various small molecule inhibitors specific to these signaling pathways were applied. Interestingly, only FAK-specific inhibitor exhibited a significant inhibitory effect on hypothermia-induced RBM3 gene transcription and protein expression. Likewise, FAK silencing using siRNA technique significantly abrogated the induction of RBM3 by hypothermia. Moreover, FAK inhibition accounted for an inactivation of Src, a known kinase downstream of FAK. Next, either the silencing of Src by siRNA or its inactivation by a chemical inhibitor, strongly blocked the induction of RBM3 by cooling. Notably, in HEK293 and PC12 cells, FAK/Src activation was also shown to be indispensable for hypothermia-stimulated RBM3 expression. Lastly, the CCK8 and Western blot assays showed that both FAK/Src inacitivation and their knockdown substantially abrogate the neuroprotective effects of mild hypothermia against rotenone in SH-SY5Y cells. These data suggest that FAK/Src signaling axis regulates the transcription of Rbm3 gene and mediates neuroprotective effects of mild hypothermia. (C) 2020 Elsevier Inc. All rights reserved.
引用
收藏
页码:240 / 247
页数:8
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