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

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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.