Involvement of both caspase-like proteases and serine proteases in apoptotic cell death induced by ricin, modeccin, diphtheria toxin, and Pseudomonas toxin
Involvement of both caspase-like proteases and serine proteases in apoptotic cell death induced by ricin, modeccin, diphtheria toxin, and Pseudomonas toxin
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DOI：
10.1093/oxfordjournals.jbchem.a022197
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发表时间：
1998-11-01
影响因子：
2.7
通讯作者：
Muramatsu, T
中科院分区：
文献类型：
--
作者：
Komatsu, N;Oda, T;Muramatsu, T
我们研究了半胱天冬酶和丝氨酸蛋白酶在 U937 细胞中由蓖麻毒素、modeccin、白喉毒素和假单胞菌毒素诱导的细胞凋亡中的作用。我们发现，在毒素诱导的细胞凋亡过程中，caspase-3 和 caspase-6 样活性增加，但 caspase-1 样活性增加。 Z-D-CH2-DCB 是一种 caspase 样抑制剂，完全抑制 caspase-3 和 caspase-6 样活性的产生，并阻断毒素诱导的细胞凋亡的所有特征：核形态变化、DNA 断裂和细胞毒性。然而，三种 caspase 特异性抑制剂 Ac-YVAD-CHO、AcDEVD-CHO 和 Ac-VEID-CRO 没有效果，即使 Ac-DEVD-CHO 和 Ac-DEVD-CHO 也没有作用。 Ac-VEID-CHO 分别抑制 caspase-3 和 caspase-6 样活性的增加。这些结果表明 caspase-3 和 caspase-6 样活性的产生是多余的，与 caspase-3 和 -6 不同的其他 caspase 可能在毒素诱导的细胞凋亡中很重要。此外，丝氨酸蛋白酶抑制剂 3,4-二氯异香豆素 (DCI) 消除了毒素引起的细胞凋亡和 DNA 断裂，而不影响 caspase-3 和 caspase-6 样活性的增加。我们的结果表明，对凋亡底物具有不同偏好的多种蛋白酶参与了毒素诱导的 U937 细胞凋亡。
We investigated the involvement of caspases and serine proteases in apoptotic cell death induced by ricin, modeccin, diphtheria toxin, and Pseudomonas toxin in U937 cells. We found that caspase-3- and caspase-6-like activities, but not caspase-1-like activity, increased during toxin-induced apoptosis. Z-D-CH2-DCB, a caspase-like inhibitor, completely inhibited the generation of caspase-3- and caspase-6-like activities and blocked all features of apoptosis induced by toxins: nuclear morphological changes,DNA fragmentation, and cytotoxicity, However, three caspase-specific inhibitors, Ac-YVAD-CHO, AcDEVD-CHO, and Ac-VEID-CRO, had no effect, even though Ac-DEVD-CHO and Ac-VEID-CHO inhibited the increased caspase-3- and caspase-6-like activity, respectively. These results suggest that the generation of caspase-3- and caspase-6-like activities is redundant, and other caspases distinct from caspase-3 and -6 may be important in toxin-induced apoptosis. Furthermore, serine protease inhibitor, 3,4-dichloroisocoumarine (DCI), abolished the apoptotic cell death and DNA fragmentation caused by toxins, without affecting the increased caspase-3- and caspase-6-like activities. Our results suggest that multiple proteases with different preferences for apoptotic substrates participate in toxin-induced apoptotic death of U937 cells.