title: RNA-binding protein RBM3 prevents NO-induced apoptosis in human neuroblastoma cells by modulating p38 signaling and miR-143.
abstract: Nitric oxide (NO)-induced apoptosis in neurons is an important cause of neurodegenerative disease in humans. The cold-inducible protein RBM3 mediates the protective effects of cooling on apoptosis induced by various insults. However, whether RBM3 protects neural cells from NO-induced apoptosis is unclear. This study aimed to investigate the neuroprotective effect of RBM3 on NO-induced apoptosis in human SH-SY5Y neuroblastoma cells. Firstly, we demonstrated that mild hypothermia (32 °C) induces RBM3 expression and confers a potent neuroprotective effect on NO-induced apoptosis, which was substantially diminished when RBM3 was silenced by siRNA. Moreover, overexpression of RBM3 exhibited a strong protective effect against NO-induced apoptosis. Signaling pathway screening demonstrated that only p38 inhibition by RBM3 provided neuroprotective effect, although RBM3 overexpression could affect the activation of p38, JNK, ERK, and AKT signaling in response to NO stimuli. Notably, RBM3 overexpression also blocked the activation of p38 signaling induced by transforming growth factor-β1. Furthermore, both RBM3 overexpression and mild hypothermia abolished the induction of miR-143 by NO, which was shown to mediate the cytotoxicity of NO in a p38-dependent way. These findings suggest that RBM3 protects neuroblastoma cells from NO-induced apoptosis by suppressing p38 signaling, which mediates apoptosis through miR-143 induction.
authors.affiliation: School of Life Science and Technology, Xinxiang Medical University, Xinxiang 453003, China.|Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, China.|Henan Key Lab of Biological Psychiatry, Second Affiliated Hospital of Xinxiang Medical University, Xinxiang 453003, China.
authors.forename: Hai-Jie
authors.initials: HJ
authors.lastname: Yang
authors.affiliation: School of Life Science and Technology, Xinxiang Medical University, Xinxiang 453003, China.|Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Ju
authors.affiliation: School of Life Science and Technology, Xinxiang Medical University, Xinxiang 453003, China.|Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, China.
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Guo
authors.affiliation: School of Life Science and Technology, Xinxiang Medical University, Xinxiang 453003, China.
authors.forename: Shuang-Ping
authors.initials: SP
authors.lastname: Ma
authors.affiliation: School of Life Science and Technology, Xinxiang Medical University, Xinxiang 453003, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: School of Life Science and Technology, Xinxiang Medical University, Xinxiang 453003, China.
authors.forename: Bin-Feng
authors.initials: BF
authors.lastname: Cheng
authors.affiliation: School of Life Science and Technology, Xinxiang Medical University, Xinxiang 453003, China.
authors.forename: Rui-Juan
authors.initials: RJ
authors.lastname: Zhuang
authors.affiliation: School of Life Science and Technology, Xinxiang Medical University, Xinxiang 453003, China.
authors.forename: Bin-Bin
authors.initials: BB
authors.lastname: Zhang
authors.affiliation: School of Life Science and Technology, Xinxiang Medical University, Xinxiang 453003, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Shi
authors.affiliation: Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, China.
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Feng
authors.affiliation: School of Life Science and Technology, Xinxiang Medical University, Xinxiang 453003, China.|Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, China.
authors.forename: Mian
authors.initials: M
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D015870:Gene Expression; D020868:Gene Silencing; D006801:Humans; D020935:MAP Kinase Signaling System; D035683:MicroRNAs / Q000235:genetics*; D009447:Neuroblastoma / Q000235:genetics* / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D013696:Temperature; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C542359:MIRN143 microRNA, human; D035683:MicroRNAs; C099506:RBM3 protein, human; D016601:RNA-Binding Proteins; D009569:Nitric Oxide; D048051:p38 Mitogen-Activated Protein Kinases