Functional analysis of phospholipid metabolizing enzymes during cell death after ischemia

2009 Fiscal Year Final Research Report

• Project/Area Number: 20890025
• Research Category: Grant-in-Aid for Young Scientists (Start-up)
• Allocation Type: Single-year Grants
• Research Field: Emergency medicine
• Research Institution: Yamagata University
• Principal Investigator: OKADA Masashi Yamagata University, 医学部, 助教 (70512614)
• Project Period (FY): 2008 – 2009
• Keywords: 虚血 / 低酸素 / ユビキチン / DGK / リン脂質 / タンパク質分解 / 細胞死

Research Abstract

In previous study, we demonstrated that diacylglycerol kinase (DGK)z which is distributed at nucleus in normal hippocampal neuron in vivo, is translocated to cytoplasm from nucleus by middle cerebral artery infarction in rat. But it is unclear that the mechanisms of ischemia induced translocation of DGKz and the physiological functions after localization in cytoplasm of DGKz. In this study, we demonstrated that DGKz nuclear export is regulated that calcium influx signaling after ischemia. Moreover, cytoplasmic DGKz is poly-ubiquitinated and degradated in hippocampal neuron in vitro and in vivo. This downregulation causes ER stress induced cell death following expression of cyclin D and cyclin E in neurons after ischema using DGKz deficient mice and siRNA knocdown study in vivo and in vitro. These datas suggest that DGKz is a downregulator of ischemic calcium signaling by inhibiting cyclin expression and cell cycle re-entry of neurons.

Research Products

• [Journal Article] Calcium fluxes cause nuclear shrinkage and the translocation of phospholipase C-delta1 into the nucleus (2010)
  • Author(s): Okada M, Taguchi K, Maekawa S, Fukami K, Yagisawa H
  • Journal Title: Neurosci Lett. 472 Pages: 188-93
  • Peer Reviewed
• [Journal Article] Influence of membrane curvature on the structure of the membrane-associated pleckstrin homology domain of phospholipase C-delta1 (2009)
  • Author(s): Uekama N, Aoki T, Maruoka T, Kurisu S, Hatakeyama A, Yamaguchi S, Okada M, Yagisawa H, Nishimura K, Tuzi S
  • Journal Title: Biochim Biophys Acta. 12 Pages: 2575-83
  • Peer Reviewed
• [Journal Article] Akt phosphorylation of merlin enhances its binding to phosphatidylinositols and inhibits the tumor-suppressive activities of Merlin (2009)
  • Author(s): Okada M, Wang Y, Jang SW, Tang X, Neri LM, Ye K
  • Journal Title: Cancer Res. 69 Pages: 4043-51
  • Peer Reviewed
• [Journal Article] Nuclear phosphoinositide signaling regulates messenger RNA export (2009)
  • Author(s): Okada M, Ye K
  • Journal Title: RNA Biol. 6 Pages: 12-6
  • Peer Reviewed
• [Journal Article] Ebp1 sumoylation, regulated by TLS/FUS E3 ligase, is required for its anti-proliferative activity (2009)
  • Author(s): Oh SM, Liu Z, Okada M, Jang SW, Liu X, Chan CB, Luo H, Ye K
  • Journal Title: Oncogene 29 Pages: 1017-30
  • Peer Reviewed
• [Journal Article] Human BRE1 is an E3 ubiquitin ligase for Ebp1 tumor suppressor (2009)
  • Author(s): Liu Z, Oh SM, Okada M, Liu X, Cheng D, Peng J, Brat DJ, Sun SY, Zhou W, Gu W, Ye K.
  • Journal Title: Mol Biol Cell. 20 Pages: 757-68
  • Peer Reviewed
• [Journal Article] Ca^<2+>-dependent nuclear accumulation of phospholipase C-d1 (2008)
  • Author(s): Yagisawa, H., Okada, M.
  • Journal Title: Neurosci.Res. 61 Pages: S39
• [Presentation] Nuclear assembly protein はDGKζの細胞内局在を制御する (2010)
  • Author(s): 岡田雅司, 後藤薫
  • Organizer: 日本解剖学会全国学術集会
  • Place of Presentation: 盛岡
  • Year and Date: 20100328-20100330
• [Presentation] DGKζ結合タンパクの探索とその性状解析 (2009)
  • Author(s): 岡田雅司, 後藤薫
  • Organizer: 日本解剖学会東北北海道支部地方会
  • Place of Presentation: 仙台
  • Year and Date: 20090926-20090927
• [Remarks] ホームページ等
  • URL: http://www.id.yamagata-u.ac.jp/AnatomyII/anaII.htm