Shimizu S, Eguchi Y, Kamiike W, Waguri S, Uchiyama Y, Matsuda H, Tsujimoto Y
The First Department of Surgery, Osaka University Medical School, Japan.
Oncogene. 1996 May 16;12(10):2045-50.
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.
氰化物、鱼藤酮或抗霉素A（化学性缺氧）对呼吸链反应的抑制会诱导坏死性细胞死亡，其特征为染色质明显完整、线粒体显著肿胀且嵴结构丧失，以及质膜完整性丧失。这些处理不会诱导凋亡性细胞死亡，凋亡性细胞死亡的定义为细胞核碎片化且染色质浓缩、细胞质碎片化或浓缩。抗凋亡蛋白Bcl-2和Bcl-xL可有效延缓化学性缺氧诱导的坏死性细胞死亡。坏死性细胞死亡也受到ICE（类）蛋白酶抑制剂的抑制，包括白细胞介素-1β转换酶（ICE），这些蛋白酶是凋亡的常见介质。这些结果表明，Bcl-2/Bcl-xL和ICE（类）蛋白酶可调节凋亡性和至少某些形式的坏死性细胞死亡。两种细胞死亡途径似乎都涉及一些共同的介质；然而，坏死性或凋亡性细胞死亡信号可能通过多种途径转导，因为Bcl-2/Bcl-xL或ICE（类）蛋白酶抑制剂在阻断坏死性细胞死亡方面相对不如在预防凋亡方面有效。
