The fresh water polyp Hydra belongs to the phylum Cnidaria, which diverged from the metazoan lineage before the appearance of bilaterians. In order to understand the evolution of apoptosis in metazoans, we have begun ...The fresh water polyp Hydra belongs to the phylum Cnidaria, which diverged from the metazoan lineage before the appearance of bilaterians. In order to understand the evolution of apoptosis in metazoans, we have begun to elucidate the molecular cell death machinery in this model organism. Based on ESTs and the whole Hydra genome assembly, we have identified 15 caspases. We show that one is activated during apoptosis, four have characteristics of initiator caspases with N-terminal DED, CARD or DD domain and two undergo autoprocessing in vitro. In addition, we describe seven Bcl-2-1ike and two Bak-like proteins. For most of the Bcl-2 family proteins, we have observed mitochondrial localization. When expressed in mammalian cells, HyBak-like 1 and 2 strongly induced apoptosis. Six of the Bcl-2 family members inhibited apoptosis induced by camptothecin in mammalian ceils with HyBcl-2-1ike 4 showing an especially strong protective effect. This protein also interacted with HyBak-like 1 in a yeast two-hybrid assay. Mutation of the conserved leucine in its BH3 domain abolished both the interaction with HyBak-like 1 and the anti-apoptotic effect. Moreover, we describe novel Hydra BH-3-only proteins. One of these interacted with Bcl-2-1ike 4 and induced apoptosis in mammalian cells. Our data indicate that the evolution of a complex network for cell death regulation arose at the earliest and simplest level of multicellular organization, where it exhibited a substantially higher level of complexity than in the protostome model organisms Caenorhabditis and Drosophila.展开更多
面神经损伤后神经元凋亡的发生、发展过程对面神经的修复具有重要意义。阐明神经元凋亡调控的分子机制,揭示神经修复的可能机理,可为临床治疗神经损伤提供实验依据。研究表明,细胞色素c(cytochrome-c,Cyt-c)、半胱氨酸天冬氨酸蛋白酶(cy...面神经损伤后神经元凋亡的发生、发展过程对面神经的修复具有重要意义。阐明神经元凋亡调控的分子机制,揭示神经修复的可能机理,可为临床治疗神经损伤提供实验依据。研究表明,细胞色素c(cytochrome-c,Cyt-c)、半胱氨酸天冬氨酸蛋白酶(cysteinyl aspartate specific protease,Caspase)家族在细胞凋亡机制中处于重要地位。本文对Cyt-c、Caspase家族中Caspase-3、Caspase-9与神经元凋亡的研究进展做一综述,进一步阐明其在面运动神经元凋亡中的表达与活化,探讨其在面神经损伤修复中的作用,为面神经损伤修复提供依据。展开更多
文摘The fresh water polyp Hydra belongs to the phylum Cnidaria, which diverged from the metazoan lineage before the appearance of bilaterians. In order to understand the evolution of apoptosis in metazoans, we have begun to elucidate the molecular cell death machinery in this model organism. Based on ESTs and the whole Hydra genome assembly, we have identified 15 caspases. We show that one is activated during apoptosis, four have characteristics of initiator caspases with N-terminal DED, CARD or DD domain and two undergo autoprocessing in vitro. In addition, we describe seven Bcl-2-1ike and two Bak-like proteins. For most of the Bcl-2 family proteins, we have observed mitochondrial localization. When expressed in mammalian cells, HyBak-like 1 and 2 strongly induced apoptosis. Six of the Bcl-2 family members inhibited apoptosis induced by camptothecin in mammalian ceils with HyBcl-2-1ike 4 showing an especially strong protective effect. This protein also interacted with HyBak-like 1 in a yeast two-hybrid assay. Mutation of the conserved leucine in its BH3 domain abolished both the interaction with HyBak-like 1 and the anti-apoptotic effect. Moreover, we describe novel Hydra BH-3-only proteins. One of these interacted with Bcl-2-1ike 4 and induced apoptosis in mammalian cells. Our data indicate that the evolution of a complex network for cell death regulation arose at the earliest and simplest level of multicellular organization, where it exhibited a substantially higher level of complexity than in the protostome model organisms Caenorhabditis and Drosophila.
文摘面神经损伤后神经元凋亡的发生、发展过程对面神经的修复具有重要意义。阐明神经元凋亡调控的分子机制,揭示神经修复的可能机理,可为临床治疗神经损伤提供实验依据。研究表明,细胞色素c(cytochrome-c,Cyt-c)、半胱氨酸天冬氨酸蛋白酶(cysteinyl aspartate specific protease,Caspase)家族在细胞凋亡机制中处于重要地位。本文对Cyt-c、Caspase家族中Caspase-3、Caspase-9与神经元凋亡的研究进展做一综述,进一步阐明其在面运动神经元凋亡中的表达与活化,探讨其在面神经损伤修复中的作用,为面神经损伤修复提供依据。
