Diacylglycerol kinase η regulates cell proliferation and its levels are elevated by glucocorticoids in undifferentiated neuroblastoma cells.

ABSTRACT

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.