Abstract
Extracelluar signal regulated kinase (ERK) or N-terminal c-Jun kinase (JNK) has been implicated as survival enhancer or death inducer in the central nervous system (CNS), respectively. Another MAP kinase, p38 MAP kinase, has been also found in the CNS cells. By the experiments using several cell types such as pheochromocytoma cell line PC12, neuroblastoma cell line N1E-115, cerebellar granule cells, endothelial cells, smooth muscle cells, it has been supposed that p38 MAP kinase might play multiple roles such as process extension, differentiation, survival, synaptic plasticity and migration, the precise function of p38 MAP kinase in the CNS cells remains unknown. To investigate the function of p38 MAP kinase in the CNS cells, first, we prepared cultured oligodendrocytes, because the predominant p38 MAP kinase expression has been reported in oligodendrocyte under physiological condition. SB202190, specific p38 MAP kinase inhibitor, dramatically reduced the number of 2', 3'-cyclic nucleotide 3'-phosphodiesterase-positive cultured oligodendrocytes by inducing the apoptosis indicated by TUNEL reaction after 24 hours, although negative pyridinyl-imidazole compound did not. Apoptosis induced by p38 MAP kinase inhibitor could be blocked by the pretreatment of JNK-inhibitor, but not caspase inhibitor, DEVD-CHO. These results suggest that p38 MAP kinase could play significant role of oligodendrocytes survival. [Jpn J Physiol 54 Suppl:S216 (2004)]