Nakano Tomoyuki, Hozumi Yasukazu, Ali Hasmat, Saino-Saito Sachiko, Kamii Hideyuki, Sato Shinya, Kayama Takamasa, Watanabe Masahiko, Kondo Hisatake, Goto Kaoru
Department of Anatomy and Cell Biology, Yamagata University School of Medicine, Iida-nishi 2-2-2, Yamagata 990-9585, Japan.
Eur J Neurosci. 2006 Mar;23(6):1427-35. doi: 10.1111/j.1460-9568.2006.04685.x.
Diacylglycerol kinase (DGK) is an enzyme that phosphorylates a second messenger diacylglycerol (DG) and is involved in a variety of pathophysiological cellular responses. We have previously reported that DGKzeta may be involved in the selective vulnerability of hippocampal CA1 neurons in transient forebrain ischemia. In this study we aimed to further elucidate functional implications of DGK isozymes in the cerebral cortex suffering from infarction using a focal ischemic model. In the early phase of 90 min of middle cerebral artery occlusion, DGKzeta-immunoreactivity is reduced rapidly in the nucleus of cortical neurons in the ischemic core, while DGKiota and other neuronal proteins such as MAP-2 and NeuN remain intact. This suggests that rapid disappearance of DGKzeta in ischemic neurons is a quite early event precedent to neuronal degeneration in response to ischemia. Furthermore, in the late inflammatory phase of infarction DGKzeta-immunoreactivity is detected in non-neuronal cells including factor VIII-positive endothelial cells and ED-1-positive phagocytic cells. The present study suggests that DGKzeta may play roles in various processes of ischemic brain damage including neuronal death and non-neuronal inflammatory response.
二酰基甘油激酶（DGK）是一种使第二信使二酰基甘油（DG）磷酸化的酶，参与多种病理生理细胞反应。我们之前报道过，DGKζ可能参与短暂性前脑缺血时海马CA1神经元的选择性易损性。在本研究中，我们旨在使用局灶性缺血模型进一步阐明DGK同工酶在梗死性大脑皮质中的功能意义。在大脑中动脉闭塞90分钟的早期阶段，缺血核心区皮质神经元细胞核中的DGKζ免疫反应性迅速降低，而DGKι和其他神经元蛋白如MAP-2和NeuN保持完整。这表明缺血神经元中DGKζ的快速消失是对缺血反应中神经元变性之前相当早的事件。此外，在梗死的晚期炎症阶段，在包括因子VIII阳性内皮细胞和ED-1阳性吞噬细胞在内的非神经元细胞中检测到DGKζ免疫反应性。本研究表明，DGKζ可能在缺血性脑损伤的各种过程中发挥作用，包括神经元死亡和非神经元炎症反应。
