Role of astrocytes in brain function

星形胶质细胞在脑功能中的作用

• 批准号: 05671805
• 负责人: NAKAHATA Norimichi
• 金额: $ 1.41万
• 依托单位: TOHOKU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05671805/
• 关键词: ASTROCYTES; PHOSPHOLIPASE C; PHOSPHOLIPASE D; PHOSPHOLIPASE A_2; PROSTAGLANDINE_2; THROMBOXANE A_2; KAMPO MEDICINE; NEUROTROPHIC FACTOR; ホスホリパーゼC; アストロサイトーマ; グリア細胞; 分化; Gタンパク質; カルシウムイオン; アラキドン酸

In order to clarify the role of astrocytes in brain function, we investigated the signal transduction in astrocytes and obtained the following results.(1) Kampo medicine such as Kakkon-to and san'o-shashin-to potently inhibit prostaglandin E_2 generation in rabbit astrocytes. Ougon (Scutellarie Radix) is a potent inhibitor of phospholipase A_2 in astrocytes. These results suggest that kampo medicines contain substances which inhibit phospholipase A_2. (2) The effect of mastoparan on signal transduction in astrocytes was investigated. Mastoparan inhibits phospholipase C in rabbit astrocytes and 1321N1 human astrocytoma cells. It is demonstrated for the first time that mastoparan activates phospholipase D in a G protein-insensitive manner in 1321N1 human astrocytoma cells. Mastoparan also activates phospholipase A_2 via Gi in rabbit astrocytes. (3) From the analysis of thromboxane A_2 (TXA_2) receptor-mediated signal transduction, TXA_2 receptor is coupled to Gq in human astrocytoma cell … More s and rabbit astrocytes. TXA_2 receptor desensitization in 1321N1 himan astrocytoma cells is divided into two steps, one is uncoupling of TXA_2 receptor and G protein, and the other is its receptor loss from cell surface (downregulation). The mRNA level of TXA_2 receptor is unchanged during TXA_2 receptor desensitization. (4) From the analysis of the effect of bioactive substances marine origin, xestoquinone activates IP_3-induced Ca^<2+> release from store site in 1321N1 human astrocytoma cells. Maitotoxin induces tyrosine kinase-mediated activation of phospholipase C-gamma isoform in a extracellular Ca^<2+>-dependent manner in 1321N1 human astrocytoma cells. 5) Supernatant of glial cell culture potently stimulated the differentiation of PC-12 cells with a potency more than nerve growth factor. The results obtained suggest that astrocytes have several important functions to control central nervous system, and signal transduction of astrocytes may contribute to understand the function of brain. Less

为了阐明星形胶质细胞在脑功能中的作用，我们研究了星形胶质细胞中的信号转导，并获得了以下结果。(1)汉方药物如葛根汤和三奥丹参-有效抑制兔星形胶质细胞产生前列腺素E_2。葛根是星形胶质细胞磷脂酶A_2的有效抑制剂。这些结果提示汉方药物中含有抑制磷脂酶A_2的物质。(2)研究了mastoparan对星形胶质细胞信号转导的影响。Mastoparan抑制兔星形胶质细胞和1321 N1人星形细胞瘤细胞中的磷脂酶C。首次证明mastoparan在1321 N1人星形细胞瘤细胞中以G蛋白不敏感的方式激活磷脂酶D。Mastoparan还通过Gi激活兔星形胶质细胞中的磷脂酶A_2。(3)从血栓素A_2（TXA_2）受体介导的信号转导分析可知，在人脑星形细胞瘤细胞中，TXA_2受体与Gq偶联 ...更多信息 s和兔星形胶质细胞。1321 N1 himan星形细胞瘤细胞TXA_2受体脱敏分为两个阶段，一是TXA_2受体与G蛋白解偶联，二是其受体从细胞表面丢失（下调）。在TXA_2受体脱敏过程中，TXA_2受体mRNA水平无明显变化。(4)海洋生物活性物质雄甾醌对IP_3诱导的1321 N1人星形细胞瘤细胞胞浆内Ca^2+释放有激活作用。在1321 N1人星形细胞瘤细胞中，Maitotoxin以细胞外Ca^<2+>依赖的方式诱导酪氨酸激酶介导的磷脂酶C-γ亚型活化。5)神经胶质细胞培养上清对PC-12细胞的促分化作用强于神经生长因子。这些结果提示星形胶质细胞在中枢神经系统的调控中具有重要的功能，而星形胶质细胞的信号转导可能有助于理解脑的功能。少

项目成果

Katsunaga Sakai, et al.: "Homologous desensitization of thromboxane A_2 receptor in 1321N1 human astrocytoma cells" J. Pharmacol. Exp. Ther.(in press).

Katsunaga Sakai 等人：“1321N1 人星形细胞瘤细胞中血栓素 A_2 受体的同源脱敏”J. Pharmacol。

Kouichi Mizuno,et al.: "Mastoparan-induced phosphatidylcholine hydrolysis by phospholipase D activation in human astrocytoma cells" Brit.J.Pharmacol.116. 2090-2096 (1995)

Kouichi Mizuno 等人：“人星形细胞瘤细胞中磷脂酶 D 激活 Mastoparan 诱导的磷脂酰胆碱水解”Brit.J.Pharmacol.116。

in press: "1995" -.

正在出版：“1995”-。

Norimichi Nakahata, et al.: "Thromboxane A_2 receptors communicate with G_<q/11> in human astrocytoma cells and rabbit cultured astrocytotes as well as human platelets" Res. Commun. Mol. Pathol. Pharmacol.87. 243-251 (1995)

Norimichi Nakahata 等人：“在人星形细胞瘤细胞和兔培养的星形细胞以及人血小板中，血栓烷 A_2 受体与 G_<q/11> 进行通信”Res。

Hiromi Ishimoto, et al.: "Difference in arachidonic acid metabolism between rabbit astrocytes and human astrocytoma cells(1321N1)" Gen. Pharmacol.(in press).

Hiromi Ishimoto 等人：“兔星形胶质细胞和人星形细胞瘤细胞 (1321N1) 之间花生四烯酸代谢的差异”Gen. Pharmacol.（出版中）。