Zeiss C J
Section of Comparative Medicine, Yale School of Medicine, 375 Congress Avenue, 126 LSOG, New Haven, CT 06520, USA.
Vet Pathol. 2003 Sep;40(5):481-95. doi: 10.1354/vp.40-5-481.
Apoptosis can be defined as a carefully regulated process, characterized by specific morphologic and biochemical features. It is initiated by both physiologic and pathologic stimuli, and its full expression requires a signaling cascade in which caspase activation plays a central role. Knockout mice lacking key genes encoding proteins constituting the core apoptotic cascade have helped us to establish the functional hierarchy of the mechanisms controlling apoptosis in animal development and, to a lesser extent, in disease. Induced mutant mice have also revealed the intimate crosstalk between apoptotic and other homeostatic pathways and have defined distinct temporal and tissue-specific roles of individual apoptotic effectors. Eliminating genes controlling caspase-dependent apoptosis can convert an apoptotic phenotype to a necrotic one, both in vitro and in vivo. This suggests that necrosis and apoptosis represent morphologic expressions of a shared biochemical network through both caspase-dependent mechanisms as well as non-caspase-dependent effectors such as cathepsin B and apoptosis-inducing factor. The cell death program, whether by apoptosis or necrosis, is mediated through an integrated cascade, which can be accessed at multiple sites, and propagated through numerous branch points. An understanding of the physiologic conditions that influence these decisions is required to adequately prevent, or induce, cell death.
细胞凋亡可被定义为一个受到严格调控的过程，其特征在于特定的形态学和生化特征。它由生理和病理刺激引发，其完整表达需要一个信号级联反应，其中半胱天冬酶激活起着核心作用。缺乏编码构成核心凋亡级联反应蛋白质的关键基因的基因敲除小鼠，帮助我们确立了在动物发育过程中以及在较小程度上在疾病中控制细胞凋亡机制的功能层次。诱导突变小鼠还揭示了凋亡途径与其他稳态途径之间的密切相互作用，并明确了各个凋亡效应器独特的时间和组织特异性作用。在体外和体内，消除控制半胱天冬酶依赖性细胞凋亡的基因可将凋亡表型转变为坏死表型。这表明坏死和凋亡代表了一个共享生化网络的形态学表现，该网络通过半胱天冬酶依赖性机制以及诸如组织蛋白酶B和凋亡诱导因子等非半胱天冬酶依赖性效应器发挥作用。细胞死亡程序，无论是通过凋亡还是坏死，都是通过一个整合的级联反应介导的，该级联反应可以在多个位点启动，并通过众多分支点传播。需要了解影响这些决定的生理条件，以便充分预防或诱导细胞死亡。
