Activation of caspase‐3‐like protease by digitonin‐treated lysosomes

FEBS Letters

Utsumi, Kozo³  Inoue, Masayasu²  Furuno, Takashi¹  Utsumi, Toshihiko⁴  Ishisaka, Rumi³  Kanno, Tomoko³  Yabuki, Munehisa³ 

[1] Department of Medicine and Gerontology, Kochi Medical School, Nankoku 783-8505, Japan;Department of Biochemistry, Osaka City University Medical School, Abeno-ku, Osaka 545-8585, Japan;Institute of Medical Science, Kurashiki Medical Center, 250 Bakuro-cho, Kurashiki 710-8522, Japan;Department of Biological Chemistry, Faculty of Agriculture, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8515, Japan

关键词: Apoptosis;    Digitonin treatment;    Caspase-3;    Cathepsin;    Lysosomal protease;    Protease inhibitor;    AMC;    7-amino-4-methyl-coumarin;    Apaf;    apoptotic protease activating factor;    ICAD;    inhibitor of caspase-activated DNase;    caspase;    cysteine protease cleaving after aspartic acid;    Cyt. c;    cytochrome c;    ICE;    interleukin-1β-converting enzyme;    NAGA;    N-acetyl-β-d-glucosaminidase;    PARP;    poly-ADP ribose polymerase;    PMSF;    phenylmethylsulfonyl fluoride;    PTP;    permeability transition pore;    S100;    cytosolic fraction of rat liver;    TPCK;    N-tosyl-l-phenylalanine chloromethyl ketone;   

DOI  :  10.1016/S0014-5793(98)01080-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Apoptosis, a naturally occurring programmed cell death or cell ‘suicide’, has been paid much attention as one of the critical mechanisms for morphogenesis and tissue remodeling. Activation of cysteine aspartases (caspases) is one of the critical steps leading to apoptosis. Although a mitochondria-mediated pathway has been postulated to be one of the activation mechanism of caspase-3, another subcellular compartment might be involved in the activation of the enzyme. The present study shows that the supernatant fraction of digitonin-treated lysosomes strongly activates Ac-DEVD-CHO inhibitable caspase-3-like protease. Activation of caspase-3-like protease by digitonin-treated lysosomal fractions was specifically suppressed by leupeptin and E-64, inhibitors of cysteine protease. These results indicate that leakage of lysosomal cysteine protease(s) into the cytosolic compartment might be involved in the activation of caspase-3-like protease.

【 授权许可】

Unknown