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Cold-inducible protein RBM3 protects neuroblastoma cells from retinoic acid-induced apoptosis via AMPK, p38 and JNK signaling

Author:
Ma, Shuang-Ping, Ju, Fei, Zhang, Ya-Ping, Shi, Xiang, Zhuang, Rui-Juan, Xue, Han, Ma, Jian, Wang, Lei, Cheng, Bin-Feng, Cao, Hong, Feng, Zhi-Wei, Wang, Mian, Yang, Hai-Jie
Source:
Journal of functional foods 2017 v.35 pp. 175-184
ISSN:
1756-4646
Subject:
apoptosis, mitogen-activated protein kinase, models, neuroprotective effect, overdose, retinoic acid, screening, signal transduction, vitamin A
Abstract:
As a result of vitamin A abuse, excessive retinoic acid can induce apoptosis in neural cells. Mild-hypothermia and cold-inducible protein RBM3 protect neural cells from apoptosis. However, whether hypothermia/RBM3 protect neural cells from retinoic acid-induced apoptosis remains unclear. The SH-SY5Y neuroblastoma cell line, a common neural cell model of apoptosis, was employed here. Interestingly, retinoic acid overdose induced apoptosis in SH-SY5Y cells, which was prevented by mild-hypothermia. When RBM3 was silenced, hypothermia-related protection was completely abolished. RBM3 overexpression significantly prevented retinoic acid-induced apoptosis. Screening of signaling pathways revealed that RBM3 overexpression markedly inhibited retinoic acid-induced upregulation of p38 and JNK signaling, and antagonized downregulation of AMPK signaling. Subsequent assays demonstrated that p38 and JNK signaling were pro-apoptotic, while AMPK was anti-apoptotic. Overall, these data showed that mild-hypothermia protects neural cells from retinoic acid-induced apoptosis via induction of RBM3, which subsequently mediates the neuroprotective effects via AMPK, p38 and JNK signaling.
Agid:
5735164