权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Regulation of the survival of mature oligodendrocytes by protein transduction of p38 MAP kinase

p38 MAP 激酶蛋白转导调节成熟少突胶质细胞的存活

基本信息

批准号：
17500262
负责人：
TAKAMATSU Ken
金额：
$ 2.24万
依托单位：
Toho University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17500262/
关键词：
Oligodendrocyte p38MAP kinase Apoptosis HIV TAT

项目摘要

p38 Mitogen-activated protein kinase (p38 MAPK) is expressed in the oligodendrocyte lineage, and its activity has been implicated in the proliferation and transition of early progenitors into late progenitors. Although p38 MAPK expression has been found in the myelin sheath, however, its role in mature oligodendrocytes remains unknown.In the present study, in order to address the role of p38 MAPK in mature oligodendrocytes, we analyzed 1. the expression of p38 MAPK in the mature oligodendrocytes, 2. the effects of p38 MAPK inhibition on the survival of mature oligodendrocytes, and 3. the effect of introduction of HIV-TAT-fused p38 MAPK protein on the survival of mature oligodendrocytes.1. Immunocytochemical and Western blot analysis revealed that mature oligodendrocytes express p38 MAPK, and a part of p38 MAPK is an active form. 2. The inhibition of p38 MAPK with specific inhibitors decreased the number of cultured mature oligodendrocyte by the induction of apoptosis, but did not alter the number of oligodendrocyte progenitor cells. These results indicate that p38 MAPK is essential for the mature oligodendrocyte survival. 3. The fusion proteins containing a cell-permeable TAT-peptide of human immunodeficiency virus could be efficiently introduced into mature oligodendrocyte. TAT-fusion protein with a dominant negative form of p38 MAPK caused the decrease in the number of mature oligodendrocyte, indicating the survival of mature oligodendrocyte can be directly regulated by protein transduction of TAT-p38 MAPK fusion proteins.We are investigating the mechanism of the survival of mature oligodendrocyte in vivo and in vitro using the cell permeable-TAT-p38 MAPK system.

p38丝裂原活化蛋白激酶（p38 MAPK）在少突胶质细胞谱系中表达，其活性与早期祖细胞向晚期祖细胞的增殖和转变有关。虽然p38 MAPK在髓鞘中有表达，但其在成熟少突胶质细胞中的作用尚不清楚。p38 MAPK在成熟少突胶质细胞中的表达; 2. p38 MAPK抑制对成熟少突胶质细胞存活的影响; 3.引入HIV-TAT融合的p38 MAPK蛋白对成熟少突胶质细胞存活的影响.免疫细胞化学和Western blot分析显示，成熟的少突胶质细胞表达p38 MAPK，并且部分p38 MAPK是活性形式。2.用特异性抑制剂抑制p38 MAPK可通过诱导凋亡减少培养的成熟少突胶质细胞的数量，但不改变少突胶质细胞祖细胞的数量。这些结果表明p38 MAPK对成熟少突胶质细胞的存活是必需的。3.含有可渗透细胞的人类免疫缺陷病毒TAT肽的融合蛋白可有效地导入成熟的少突胶质细胞。本研究利用细胞可渗透的TAT-p38 MAPK系统，在体内、外研究成熟少突胶质细胞存活的机制。