Kitamura Yoshihisa, Inden Masatoshi, Miyamura Atsushi, Kakimura Jun-ichi, Taniguchi Takashi, Shimohama Shun
Department of Neurobiology, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan.
Neurosci Lett. 2002 Nov 15;333(1):25-8. doi: 10.1016/s0304-3940(02)00964-3.
Recently, it has been shown that rotenone, a specific inhibitor of mitochondrial complex I, is a useful tool in animal models of Parkinson's disease, but the mechanism of rotenone-induced neuronal death is not fully understood. In human neuroblastoma SH-SY5Y cells, rotenone induced the degradation of procaspases-12, -9 and -3, followed by cleavage of poly (adenosine diphosphate-ribose) polymerase, DNA fragmentation and cell death. Pretreatment with phorbol-12-myristate-13-acetate inhibited the rotenone-induced decrease in procaspases-9 and -3, but not that in procaspase-12. In contrast, benzyloxycarbonyl-Val-Ala-Asp(OCH(3))-CH(2)F inhibited the decrease in procaspase-12, but not those in procaspases-9 and -3 in this study. These results suggest that rotenone may induce activation of both mitochondria- and endoplasmic reticulum-dependent caspases in human SH-SY5Y cells.
最近的研究表明，鱼藤酮作为线粒体复合体I的一种特异性抑制剂，在帕金森病动物模型中是一种有用的工具，但鱼藤酮诱导神经元死亡的机制尚未完全明确。在人神经母细胞瘤SH-SY5Y细胞中，鱼藤酮可诱导procaspases-12、-9和-3的降解，随后多聚（二磷酸腺苷核糖）聚合酶裂解、DNA片段化及细胞死亡。用佛波醇-12-肉豆蔻酸酯-13-乙酸酯预处理可抑制鱼藤酮诱导的procaspases-9和-3的减少，但不能抑制procaspase-12的减少。相反，在本研究中，苄氧羰基-Val-Ala-Asp（OCH(3)）-CH(2)F可抑制procaspase-12的减少，但不能抑制procaspases-9和-3的减少。这些结果表明，鱼藤酮可能在人SH-SY5Y细胞中诱导线粒体和内质网依赖性半胱天冬酶的激活。
