An Inhibitor of p38 and JNK MAP Kinases Prevents Activationof Caspase and Apoptosis of Cultured Cerebellar Granule Neurons

この論文にアクセスする

この論文をさがす

著者

抄録

Both p38 mitogen-activated protein kinase (p38) and c-Jun N-terminal kinase (JNK) are known to play important roles in neuronal apoptosis. However, the relationship between these kinases and caspases, another key mediator of apoptosis, is unclear. In the present study, we investigated the possible effects of SB203580 [(4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-imidazole), an inhibitor of p38, on caspase activation and apoptosis of cultured rat cerebellar granule neurons. In granule neurons, SB203580 prevented apoptosis that was induced by lowering the concentration of KCl in the culture medium for 24 hr. SB203580 also prevented augmentation of caspase-3-like protease activity at 8 hr after the low KCl treatment. The IC<SUB>50</SUB> values of SB203580 for both events were between 3 μM and 10 μM. Expression and phosphorylation of c-Jun, potently induced by low KCl treatment, were prevented by SB203580 at 10 μM. Z-Asp-CH<SUB>2</SUB>-DCB, a caspase inhibitor with anti-apoptotic activity, did not inhibit the induction and phosphorylation of c-Jun. Granule neurons displayed high levels of p38 and JNK activities. SB203580 inhibited not only p38 but also JNK activities extracted from granule neurons. These results suggest that activation of c-Jun by p38 and/or JNK mediates the activation of caspase in the low KCl-induced apoptosis in cerebellar granule neurons.

収録刊行物

  • The Japanese journal of pharmacology

    The Japanese journal of pharmacology 79(3), 369-378, 1999-03-01

    The Japanese Pharmacological Society

参考文献:  52件中 1-52件 を表示

被引用文献:  1件中 1-1件 を表示

各種コード

  • NII論文ID(NAID)
    10008682966
  • NII書誌ID(NCID)
    AA00691188
  • 本文言語コード
    ENG
  • 資料種別
    REV
  • ISSN
    00215198
  • NDL 記事登録ID
    4699268
  • NDL 雑誌分類
    ZS51(科学技術--薬学)
  • NDL 請求記号
    Z53-D199
  • データ提供元
    CJP書誌  CJP引用  NDL  J-STAGE 
ページトップへ