Inhibition of p38 mitogen-activated protein kinase-induced apoptosis in cultured mature oligodendrocytes using SB2021.90 and SB203580
Inhibition of p38 mitogen-activated protein kinase-induced apoptosis in cultured mature oligodendrocytes using SB2021.90 and SB203580
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DOI：
10.1016/j.neuint.2007.03.005
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发表时间：
2007-07-01
影响因子：
4.2
通讯作者：
Takamatsu, Ken
中科院分区：
文献类型：
--
作者：
Hamanoue, Makoto;Sato, Kenichiro;Takamatsu, Ken
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，为了研究p38 MAPK在成熟少突胶质细胞中的作用，本研究将p38 MAPK的选择性抑制剂SB 202190和SB 203580加入到成熟少突胶质细胞的原代培养物中。在暴露于抑制剂24小时后，A2 B5阳性祖细胞的外观和数量没有变化。然而，与用SB 203580的阴性类似物SB 202474处理的对照细胞相比，2 '，3'-环核苷酸-3 '-磷酸水解酶阳性的成熟少突胶质细胞消失，并且活细胞的数量减少。末端脱氧核苷酸转移酶介导的dUTP缺口末端标记阳性细胞核的数量和caspase-3/7的活性的增加被检测到16小时后，暴露于抑制剂，从而导致成熟的少突胶质细胞死亡，由于凋亡。使用分化的大鼠少突胶质细胞前体细胞（OPC）系，中央胶质细胞-4（CG-4）获得了类似的结果。这些发现表明p38 MAPK对成熟少突胶质细胞的存活至关重要。(C)2007爱思唯尔有限公司保留所有权利。
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, selective inhibitors of p38 MAPK, SB202190, and SB203580 were added to primary cultures of mature oligodendrocytes. After 24 h of exposure to the inhibitors, the appearance, and number of A2B5-positive progenitors were unchanged. However, the 2',3'-cyclic nucleotide-3'-phosphohydrolase-positive mature oligodendrocytes disappeared, and the numbers of living cells decreased in comparison to the control cells treated with SB202474, a negative analog of SB203580. Increases in the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive nuclei and in the activity of caspase-3/7 were detected 16 h after exposure to the inhibitors, thus causing the mature oligodendrocytes to die due to apoptosis. Similar results were obtained using a differentiated rat oligodendrocyte precursor cell (OPC) line, central glia-4 (CG-4). These findings indicate that p38 MAPK is vital for mature oligodendrocyte survival. (C) 2007 Elsevier Ltd. All rights reserved.