Mild Hypothermia Prevents NO-Induced Cytotoxicity in Human Neuroblastoma Cells Via Induction of COX-2
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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.
KeywordsMild hypothermia RBM3 COX2 Neuroprotection Nitric oxide
We thank Medsci (www.medsci.com) for the linguistic assistance during the preparation of this manuscript.
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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Conflict of Interest
The authors declare that they have no conflict of interest.
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