Suppression of okadaic acid‐induced apoptosis by overexpression of calpastatin in human UVr‐1 cells

FEBS Letters

Kita, Kazuko²  Chi, Xiao-Jun²  Maki, Masatoshi¹  Suzuki, Nobuo²  Nomura, Jun²  Hiwasa, Takaki²  Sugaya, Shigeru² 

[1] Department of Applied Biological Sciences, School of Agricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan;Department of Biochemistry, School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8670, Japan

关键词: Apoptosis;    Okadaic acid;    Calpastatin;    c-Jun;    ALLN;    acetyl-Leu-Leu-norleucinal;    DMSO;    dimethylsulfoxide;    JNK;    Jun N-terminal kinase;    IC50;    half-maximum inhibition concentration;    MAP kinase;    mitogen-activated protein kinase;    MTT;    3-(4;    5-dimethylthiazol-2-yl)-2;    5-diphenyltetrazolium bromide;    OA;    okadaic acid;    SAPK;    stress-activated protein kinase;   

DOI  :  10.1016/S0014-5793(99)01281-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Proteolytic systems have various involvements in apoptotic pathways. To understand the role of calpain in apoptosis, calpastatin, a specific inhibitor of calpain, was overexpressed in human UV^r-1 fibroblasts by transfection of its cDNA. The elevated expression of calpastatin resulted in decreased survival in the presence of okadaic acid (OA) but in no apparent alteration in the sensitivity toward other drugs such as 5-fluorouracil, mitomycin C and methotrexate. After treatment with OA, a typical apoptotic DNA ladder was observed in control vector-transfected cells but not in calpastatin-transfected cells. This indicates that OA-induced apoptosis was suppressed by overexpression of calpastatin. Further immunoblot analysis showed that the OA-induced hyperphosphorylation of c-Jun was inhibited in calpastatin-transfected cells. This might be involved in the resistance to OA-induced cell death in calpastatin-overproducing cells.

【 授权许可】

Unknown