Simizu S, Umezawa K, Takada M, Arber N, Imoto M
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan.
Exp Cell Res. 1998 Jan 10;238(1):197-203. doi: 10.1006/excr.1997.3823.
In our previous studies (S. Simizu, et al., 1996, Cancer Res. 56, 4978-4982), we reported that apoptosis of human small cell lung carcinoma (SCLC) cells induced by protein tyrosine kinase inhibitors, such as erbstatin and herbimycin A, was mediated by H2O2 via a newly synthesized protein(s). In the present study, we demonstrated that induction of apoptosis by erbstatin resulted in activation of caspase-3(-like) proteases, which are interleukin-1 beta-converting enzyme family proteases (caspases) and that inhibition of these protease activities reduced the extent of cell death and H2O2 generation. We also demonstrated that expression of apoptotic protein Bax was induced by erbstatin. Erbstatin-induced Bax expression was inhibited by the inhibitor of caspase-3(-like) proteases. These results indicate that generation of intracellular H2O2 and Bax expression in tyrosine kinase inhibitor-induced apoptosis were modulated by the activation of caspase-3(-like) proteases in SCLC cells.
在我们之前的研究中（S. Simizu等人，1996年，《癌症研究》56卷，4978 - 4982页），我们报道了蛋白酪氨酸激酶抑制剂（如埃伯他汀和赫比霉素A）诱导人小细胞肺癌（SCLC）细胞凋亡是由H2O2通过一种新合成的蛋白质介导的。在本研究中，我们证明埃伯他汀诱导的凋亡导致了caspase - 3（类）蛋白酶的激活，这些蛋白酶属于白细胞介素 - 1β转化酶家族蛋白酶（半胱天冬酶），并且这些蛋白酶活性的抑制降低了细胞死亡程度和H2O2的产生。我们还证明埃伯他汀诱导了凋亡蛋白Bax的表达。埃伯他汀诱导的Bax表达被caspase - 3（类）蛋白酶抑制剂所抑制。这些结果表明，在SCLC细胞中，酪氨酸激酶抑制剂诱导的细胞凋亡过程中，细胞内H2O2的产生和Bax的表达是由caspase - 3（类）蛋白酶的激活所调节的。
