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Histochemistry and Cell Biology

, Volume 137, Issue 4, pp 499–511 | Cite as

NMDA receptor-mediated Ca2+ influx triggers nucleocytoplasmic translocation of diacylglycerol kinase ζ under oxygen–glucose deprivation conditions, an in vitro model of ischemia, in rat hippocampal slices

  • Yusuke Suzuki
  • Yoshihiko Yamazaki
  • Yasukazu Hozumi
  • Masashi Okada
  • Toshiaki Tanaka
  • Ken Iseki
  • Nobuo Ohta
  • Masaru Aoyagi
  • Satoshi Fujii
  • Kaoru GotoEmail author
Original Paper

Abstract

Diacylglycerol kinase (DGK) plays a key role in pathophysiological cellular responses by regulating the levels of a lipid messenger diacylglycerol. Of DGK isozymes, DGKζ localizes to the nucleus in various cells such as neurons. We previously reported that DGKζ translocates from the nucleus to the cytoplasm in hippocampal CA1 pyramidal neurons after 20 min of transient forebrain ischemia. In this study, we examined the underlying mechanism of DGKζ translocation using hippocampal slices exposed to oxygen-glucose deprivation (OGD) to simulate an ischemic model of the brain. DGKζ-immunoreactivity gradually changed from the nucleus to the cytoplasm in CA1 pyramidal neurons after 20 min of OGD and was never detected in the nucleus after reoxygenation. Intriguingly, DGKζ was detected in the nucleus at 10 min OGD whereas the following 60 min reoxygenation induced complete cytoplasmic translocation of DGKζ. Morphometric analysis revealed that DGKζ cytoplasmic translocation correlated with nuclear shrinkage indicative of an early process of neuronal degeneration. The translocation under OGD conditions was blocked by NMDA receptor (NMDAR) inhibitor, and was induced by activation of NMDAR. Chelation of the extracellular Ca2+ blocked the translocation under OGD conditions. These results show that DGKζ cytoplasmic translocation is triggered by activation of NMDAR with subsequent extracellular Ca2+ influx. Furthermore, inhibition of PKC activity under OGD conditions led to nuclear retention of DGKζ in about one-third of the neurons, suggesting that PKC activity partially regulates DGKζ cytoplasmic translocation. These findings provide clues to guide further investigation of glutamate excitotoxicity mechanisms in hippocampal neurons.

Keywords

Diacylglycerol kinase Hippocampal slices NMDA receptor Ca2+ influx OGD PKC 

Notes

Acknowledgments

We are thankful to Mr. Kenya Kaneko for his technical help in preparing hippocampal slices. This work was supported by Grants-in-Aid from The Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan (YY, YH, MO, KI, SF, KG).

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Yusuke Suzuki
    • 1
    • 2
  • Yoshihiko Yamazaki
    • 3
  • Yasukazu Hozumi
    • 1
  • Masashi Okada
    • 1
  • Toshiaki Tanaka
    • 1
  • Ken Iseki
    • 4
  • Nobuo Ohta
    • 2
  • Masaru Aoyagi
    • 2
  • Satoshi Fujii
    • 3
  • Kaoru Goto
    • 1
    Email author
  1. 1.Department of Anatomy and Cell BiologyYamagata University School of MedicineYamagataJapan
  2. 2.Department of OtolaryngologyYamagata University School of MedicineYamagataJapan
  3. 3.Department of PhysiologyYamagata University School of MedicineYamagataJapan
  4. 4.Department of Emergency and Critical Care MedicineYamagata University School of MedicineYamagataJapan

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