Nakano Tomoyuki, Iseki Ken, Hozumi Yasukazu, Kawamae Kaneyuki, Wakabayashi Ichiro, Goto Kaoru
Department of Anatomy and Cell Biology, Yamagata University School of Medicine, Yamagata 990-9585, Japan.
Neurosci Lett. 2009 Sep 18;461(2):110-5. doi: 10.1016/j.neulet.2009.06.001. Epub 2009 Jun 9.
Diacylglycerol kinase (DGK) is an enzyme which phosphorylates a second messenger diacylglycerol and consists of a family of isozymes that differ in terms of structural motifs, enzymological property, and cell and tissue distribution. One of the isozymes, DGKzeta was originally shown to be expressed in various kinds of neurons under physiological conditions. However, we unexpectedly found that under pathological conditions, such as cerebral infarction, DGKzeta-immunoreactivity is detected in non-neuronal cells, although it remained to be elucidated in detail which cell types are responsible for the induced expression of DGKzeta in this setting. To further elucidate functional implications of DGKzeta in non-neuronal cells we performed detailed immunohistochemical analysis of DGKzeta using rat brain cryoinjury model. As early as 1h after cryoinjury, DGKzeta-immunoreactivity was greatly decreased in the afflicted cerebral cortex and almost disappeared in the necrotic core. On day 7 after cryoinjury, however, DGKzeta-immunoreactivity reappeared in this area. DGKzeta-immunoreactivity was clearly detected in Iba1-immunoreactive cells of an oval or ameboid shape in the scar region, which represent activated microglia and/or macrophages. On the other hand, DGKzeta-immunoreactivity was not detected in Iba1-immunoreactive, resting microglia of ramified and dendritic configuration in the intact cortex. Furthermore, DGKzeta-immunoreactive cells were also positive for a microglia marker GLUT5 in the scar region, but never for an astrocyte marker GFAP. Taken together, the present study reveals that DGKzeta is induced in activated microglia in brain trauma, suggesting the functional significance of DGKzeta in this process.
二酰甘油激酶（DGK）是一种使第二信使二酰甘油磷酸化的酶，由一系列同工酶组成，这些同工酶在结构基序、酶学性质以及细胞和组织分布方面存在差异。其中一种同工酶DGKζ最初被证明在生理条件下在各种神经元中表达。然而，我们意外地发现，在病理条件下，如脑梗死，在非神经元细胞中可检测到DGKζ免疫反应性，尽管在此情况下究竟哪些细胞类型负责DGKζ的诱导表达仍有待详细阐明。为了进一步阐明DGKζ在非神经元细胞中的功能意义，我们使用大鼠脑冷冻损伤模型对DGKζ进行了详细的免疫组织化学分析。冷冻损伤后1小时，受损大脑皮层中的DGKζ免疫反应性大幅下降，在坏死核心几乎消失。然而，在冷冻损伤后第7天，该区域再次出现DGKζ免疫反应性。在瘢痕区域呈椭圆形或阿米巴样的Iba1免疫反应性细胞中可清晰检测到DGKζ免疫反应性，这些细胞代表活化的小胶质细胞和/或巨噬细胞。另一方面，在完整皮层中呈分支状和树突状的Iba1免疫反应性静息小胶质细胞中未检测到DGKζ免疫反应性。此外，瘢痕区域中DGKζ免疫反应性细胞对小胶质细胞标志物GLUT5也呈阳性，但对星形胶质细胞标志物GFAP则从未呈阳性。综上所述，本研究表明在脑创伤中活化的小胶质细胞中诱导表达DGKζ，提示DGKζ在此过程中的功能意义。
