Diacylglycerol kinase ζ generates dipalmitoyl-phosphatidic acid species during neuroblastoma cell differentiation

Satoru Mizuno, Sayaka Kado, Kaoru Goto, Daisuke Takahashi, Fumio Sakane

Research output: Contribution to journalArticle

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Abstract

Phosphatidic acid (PA) is one of the phospholipids composing the plasma membrane and acts as a second messenger to regulate a wide variety of important cellular events, including mitogenesis, migration and differentiation. PA consists of various molecular species with different acyl chains at the sn-1 and sn-2 positions. However, it has been poorly understood what PA molecular species are produced during such cellular events. Here we identified the PA molecular species generated during retinoic acid (RA)-induced neuroblastoma cell differentiation using a newly established liquid chromatography/mass spectrometry (LC/MS) method. Intriguingly, the amount of 32:0-PA species was dramatically and transiently increased in Neuro-2a neuroblastoma cells 24-48 h after RA-treatment. In addition, 30:0- and 34:0-PA species were also moderately increased. Moreover, similar results were obtained when Neuro-2a cells were differentiated for 24 h by serum starvation. MS/MS analysis revealed that 32:0-PA species contains two palmitic acids (16:0 s). RT-PCR analysis showed that diacylglycerol kinase (DGK) δ and DGKζ were highly expressed in Neuro-2a cells. The silencing of DGKζ expression significantly decreased the production of 32:0-PA species, whereas DGKδ-siRNA did not. Moreover, neurite outgrowth was also markedly attenuated by the deficiency of DGKζ. Taken together, these results indicate that DGKζ exclusively generates very restricted PA species, 16:0/16:0-PA, and up-regulates neurite outgrowth during the initial/early stage of neuroblastoma cell differentiation.

Original languageEnglish
Pages (from-to)352-359
Number of pages8
JournalBiochemistry and Biophysics Reports
Volume8
DOIs
Publication statusPublished - Dec 2016

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Diacylglycerol Kinase
Phosphatidic Acids
Neuroblastoma
Cell Differentiation
Tretinoin
Palmitic Acids
dipalmitoylphosphatidic acid
Liquid chromatography
Second Messenger Systems
Cell membranes
Starvation
Liquid Chromatography
Small Interfering RNA
Mass spectrometry
Mass Spectrometry
Phospholipids
Up-Regulation
Cell Membrane

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Diacylglycerol kinase ζ generates dipalmitoyl-phosphatidic acid species during neuroblastoma cell differentiation. / Mizuno, Satoru; Kado, Sayaka; Goto, Kaoru; Takahashi, Daisuke; Sakane, Fumio.

In: Biochemistry and Biophysics Reports, Vol. 8, 12.2016, p. 352-359.

Research output: Contribution to journalArticle

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AU - Kado, Sayaka

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AU - Takahashi, Daisuke

AU - Sakane, Fumio

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