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| Content Provider | Springer Nature Link |
|---|---|
| Author | Suzuki, Yusuke Yamazaki, Yoshihiko Hozumi, Yasukazu Okada, Masashi Tanaka, Toshiaki Iseki, Ken Ohta, buo Aoyagi, Masaru Fujii, Satoshi Goto, Kaoru |
| Copyright Year | 2012 |
| 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. |
| Starting Page | 499 |
| Ending Page | 511 |
| Page Count | 13 |
| File Format | |
| ISSN | 09486143 |
| Journal | Histochemistry and Cell Biology |
| Volume Number | 137 |
| Issue Number | 4 |
| e-ISSN | 1432119X |
| Language | English |
| Publisher | Springer-Verlag |
| Publisher Date | 2012-01-11 |
| Publisher Place | Berlin/Heidelberg |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Diacylglycerol kinase Hippocampal slices NMDA receptor Ca2+ influx OGD PKC Anatomy Medicine/Public Health |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Histology Molecular Biology Medical Laboratory Technology |
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