Diacylglycerol kinase inhibitor R59022-induced autophagy and apoptosis in the neuronal cell line NG108-15

Tsuyoshi Takita, Tsubasa Konuma, Miki Hanazato, Hiroko Inoue

    Research output: Contribution to journalArticle

    8 Citations (Scopus)

    Abstract

    Phosphatidic acid (PA) is a lipid second messenger and is believed to be involved in cell proliferation and survival. PA is mainly produced by phospholipase D (PLD) and diacylglycerol kinase (DGK). Elevated PLD activity is believed to suppress apoptosis via activation of the mammalian target of rapamycin (mTOR). On the other hand, DGK inhibition has been demonstrated to induce apoptosis, but it is unclear whether DGK can regulate mTOR. Here, we investigated whether DGK inhibition can induce apoptosis and autophagy in neuronal cells, since mTOR is a key mediator of autophagy and the simultaneous activation of apoptosis and autophagy has been detected. A DGK inhibitor, R59022 induced autophagy and apoptosis without serum in NG108-15 cells. Autophagy preceded apoptosis, and apoptosis inhibition did not affect R59022-induced autophagy. R59022-induced autophagy was inhibited by exogenous PA, and protein kinase C activation and increases in intracellular Ca2+ levels, which are assumed to be caused by diacylglycerol accumulation, did not appear to be involved in R59022-induced autophagy. We also investigated the effects of R59022 on mTOR signaling pathway, and found that the pathway was not inhibited by R59022. These results imply that DGK plays an important role in cell survival via mTOR-independent mechanism.

    Original languageEnglish
    Pages (from-to)197-201
    Number of pages5
    JournalArchives of Biochemistry and Biophysics
    Volume509
    Issue number2
    DOIs
    Publication statusPublished - 2011 May 15

    Keywords

    • Apoptosis
    • Autophagy
    • Diacylglycerol kinase
    • Mammalian target of rapamycin
    • NG108-15 cells
    • Phosphatidic acid

    ASJC Scopus subject areas

    • Biochemistry
    • Biophysics
    • Molecular Biology

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