Retardation of chemical hypoxia-induced necrotic cell death by Bcl-2 and ICE inhibitors: possible involvement of common mediators in apoptotic and necrotic signal transductions.
Retardation of chemical hypoxia-induced necrotic cell death by Bcl-2 and ICE inhibitors: possible involvement of common mediators in apoptotic and necrotic signal transductions.
复制标题
DOI：
--
复制
发表时间：
1996-05
期刊：
影响因子：
8
通讯作者：
S. Shimizu;Y. Eguchi;W. Kamiike;S. Waguri;Y. Uchiyama;Hikaru Matsuda;Y. Tsujimoto
中科院分区：
文献类型：
--
作者：
S. Shimizu;Y. Eguchi;W. Kamiike;S. Waguri;Y. Uchiyama;Hikaru Matsuda;Y. Tsujimoto
氰化物、鱼藤酮或抗霉素A（化学缺氧）对呼吸链反应的抑制诱导坏死性细胞死亡，其特征为明显完整的染色质、显著的线粒体肿胀伴嵴结构丧失和质膜完整性丧失。所述处理不诱导凋亡性细胞死亡，如通过具有浓缩染色质的碎裂核、碎裂或浓缩的细胞质所定义的。抗凋亡蛋白Bcl-2和Bcl-xL有效地延缓了化学缺氧诱导的坏死细胞死亡。ICE（-样）蛋白酶的抑制剂也能延缓坏死细胞的死亡，包括白细胞介素-1 β转化酶（ICE），这是凋亡的常见介质。这些结果表明Bcl-2/Bcl-xL和ICE（-样）蛋白酶调节凋亡和至少某些形式的坏死细胞死亡。两种细胞死亡途径似乎都涉及一些共同的介质;然而，坏死或凋亡细胞死亡信号可能通过多种途径转导，因为Bcl-2/ Bcl-xL或ICE（-样）蛋白酶抑制剂在阻断坏死细胞死亡方面的效力相对低于预防凋亡。
Inhibition of the respiratory chain reaction by cyanide, rotenone or antimycin A (chemical hypoxia) induces necrotic cell death characterized by apparently intact chromatin, remarkable mitochondrial swelling with loss of crista structure, and loss of plasma membrane integrity. The treatments induce no apoptotic cell death, as defined by fragmented nuclei with condensed chromatin, fragmented or condensed cytoplasm. The anti-apoptotic proteins Bcl-2 and Bcl-xL effectively retard the chemical hypoxia-induced necrotic cell death. The necrotic cell death is also retarded by inhibitors of ICE(-like) proteases, including interleukin-1beta converting enzyme (ICE), which are common mediators of apoptosis. These results indicate that Bcl-2/Bcl-xL and ICE(-like) proteases modulate apoptotic and at least some forms of necrotic cell death. Both cell death pathways appear to involve some common mediators; however necrotic or apoptotic cell death signals might be transduced through multiple pathways, because Bcl-2/ Bcl-xL or inhibitors of ICE(-like) proteases are relatively less potent in blocking necrotic cell death than in preventing apoptosis.