期刊论文详细信息
FEBS Letters
Hypoxia induces apoptosis in human neuroblastoma SK‐N‐MC cells by caspase activation accompanying cytochrome c release from mitochondria
Nomura, Yasuyuki1  Uehara, Takashi1  Araya, Runa1 
[1] Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
关键词: Neuronal cell;    Hypoxia;    Apoptosis;    Caspase;    Cytochrome c;    Z-Asp-CH2-DCB;    benzyloxycarbonyl-Asp-CH2OC(O)-2;    6-dichlorobenzene;    CPP32;    cysteine protease p32;    DEVD-MCA;    N-acetyl-Asp-Glu-Val-Asp-4-methylcoumaryl-7-amide;    YVAD-MCA;    N-acetyl-Tyr-Val-Ala-Asp-4-methylcoumaryl-7-amide;    AMC;    7-amino-4-methylcoumarin;    ICE;    interleukin-1β-converting enzyme;    ICH-1;    ICE and CED-3 homolog 1;    PARP;    poly(ADP-ribose) polymerase;    PBS;    phosphate-buffered saline;    PMSF;    phenylmethylsulfonyl fluoride;   
DOI  :  10.1016/S0014-5793(98)01363-5
学科分类:生物化学/生物物理
来源: John Wiley & Sons Ltd.
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【 摘 要 】

We have attempted to elucidate the mechanism of apoptotic cell death induced by hypoxia (very low oxygen conditions) in neuronal cells. Human neuroblastoma SK-N-MC cells under hypoxic conditions resulted in apoptosis in a time-dependent manner estimated by DNA fragmentation assay and nuclear morphology stained with fluorescent chromatin dye. Pretreatment with Z-Asp-CH2-DCB, a caspase inhibitor, suppressed the DNA ladder in response to hypoxia in a concentration-dependent manner. An increase in caspase-3-like protease (DEVDase) activity was observed during apoptosis, but no caspase-1 activity (YVADase) was detected. To confirm the involvement of caspase-3 during apoptosis, Western blot analysis was performed using anti-caspase-3 antibody. The 20- and 17-kDa proteins, corresponding to the active products of caspase-3, were generated in hypoxia-challenged lysates in which processing of the full length form of caspase-3 was evident. With a time course similar to this caspase-3 activation, hypoxic stress caused the cleavage of PARP, yielding an 85-kDa fragment typical of caspase activity. In addition, caspase-2 was also activated by hypoxia, and the stress elicited the release of cytochrome c into the cytosol during apoptosis. These results suggest that caspase activation and cytochrome c release play roles in hypoxia-induced neuronal apoptosis.

【 授权许可】

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