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

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的增殖和向晚期祖细胞的转变有关。尽管在髓鞘中发现了p38 MAPK的表达，但其在成熟少突胶质细胞中的作用尚不清楚。在本研究中，为了解决p38 MAPK在成熟少突胶质细胞中的作用，我们分析了1。2. 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；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，成熟少突胶质细胞表达p38 MAPK，且部分p38 MAPK为活性形式。2. 特异性抑制剂抑制p38 MAPK通过诱导凋亡减少培养的成熟少突胶质细胞的数量，但未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至关重要。3. 融合蛋白含有细胞可渗透的人免疫缺陷病毒tat -肽，可有效导入成熟少突胶质细胞。p38 MAPK显性阴性形式的tat融合蛋白导致成熟少突胶质细胞数量减少，表明成熟少突胶质细胞的存活可通过TAT-p38 MAPK融合蛋白的蛋白转导直接调节。我们正在利用细胞通透性- tat -p38 MAPK系统研究成熟少突胶质细胞在体内和体外的存活机制。

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.