Diacylglycerol kinase η regulates cell proliferation and its levels are elevated by glucocorticoids in undifferentiated neuroblastoma cells
Diacylglycerol kinase η regulates cell proliferation and its levels are elevated by glucocorticoids in undifferentiated neuroblastoma cells
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DOI：
10.1016/j.bbrc.2022.02.100
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发表时间：
2022-03-03
影响因子：
3.1
通讯作者：
Sakane，Fumio
中科院分区：
文献类型：
--
作者：
Masuda，Yuka;Murakami，Chiaki;Sakane，Fumio
被全基因组关联研究反复提示与双相情感障碍(BPD)相关的DGKη基因敲除小鼠表现出类似于BPD躁狂期的异常行为。慢性压力也与情绪症状的变化有关，包括BPD。在本研究中，我们分析了糖皮质激素应激激素曲安奈德和地塞米松对神经母细胞瘤细胞株Neuro-2a和SH-SY5Y中DGKη蛋白水平的影响。在未分化的Neuro-2a和SH-SY5Y细胞中，地塞米松和地塞米松显著增加DGKη的蛋白水平，而在分化的神经母细胞瘤细胞中无此作用。为了研究DGKη在未分化神经母细胞瘤细胞中的功能，我们利用成簇的规则间隔回文重复序列/Caspase9系统建立了DGKη缺陷的SH-SY5Y细胞。值得注意的是，DGKη缺陷的SH-SY5Y细胞的增殖明显减弱，伴随着磷酸化的细胞外信号调节激酶水平的下降。综上所述，这些结果表明，糖皮质激素应激激素增加了未分化神经母细胞瘤细胞中DGKη的水平，并调节了细胞增殖。
Knockout mice of diacylglycerol kinase (DGK) η, which has been repeatedly suggested to be associated with bipolar disorder (BPD) by genome-wide association studies, exhibited abnormal behaviors similar to the manic phase of BPD. Chronic stress is also linked to changes in mood symptoms, including BPD. In the present study, we analyzed the effects of the glucocorticoid stress hormones, triamcinolone acetonide (TAA) and dexamethasone (DEX), on DGKη protein levels in neuroblastoma cell lines, Neuro-2a and SH-SY5Y. The protein levels of DGKη were significantly increased in the undifferentiated Neuro-2a and SH-SY5Y cells by TAA and DEX, but not in the differentiated neuroblastoma cells. To assess the functions of DGKη in undifferentiated neuroblastoma cells, we established DGKη-deficient SH-SY5Y cells using the clustered regularly interspaced palindromic repeat/caspase 9 system. Notably, proliferation of DGKη-deficient SH-SY5Y cells was markedly attenuated, concomitant with the decrease in levels of phosphorylated extracellular signal-regulated kinase. Taken together, these results suggest that DGKη levels are increased in undifferentiated neuroblastoma cells by glucocorticoid stress hormones and regulate cell proliferation.