Evidence That Wallerian Degeneration and Localized Axon Degeneration Induced by Local Neurotrophin Deprivation Do Not Involve Caspases
Evidence That Wallerian Degeneration and Localized Axon Degeneration Induced by Local Neurotrophin Deprivation Do Not Involve Caspases
复制标题
局部神经营养蛋白剥夺引起的沃勒变性和局部轴突变性不涉及半胱天冬酶的证据
作者：
J. Finn;M. Weil;Fabienne Archer;R. Siman;A. Srinivasan;M. Raff
在各种代谢、毒性和炎症性疾病以及正常发育过程中，轴突的选择性变性可能会因损伤而发生，而母体神经元不会死亡。最近的证据表明，某些形式的轴突变性涉及主动和受调节的自我毁灭程序，而不是被动的“消瘦”，在这方面和其他方面类似于细胞凋亡。在这里，我们研究选择性轴突变性是否取决于介导细胞凋亡的一些分子机制，即半胱氨酸蛋白酶的半胱天冬酶家族。我们关注选择性轴突变性的两种模型：横切轴突的沃勒变性和神经营养蛋白局部剥夺引起的局部轴突变性。我们发现，在这两种形式的变性过程中，caspase-3 在轴突中都没有被激活，尽管它在相同神经元的垂死细胞体中被激活。此外，半胱天冬酶抑制剂不抑制或延缓任何一种形式的轴突变性，尽管它们抑制相同神经元的凋亡。最后，我们无法通过免疫细胞化学方法检测 caspase-3 及其近亲的裂解底物，也无法通过生化方法检测发生华勒变性的轴突中的 caspase 活性。我们的结果表明，神经元至少包含两种分子上不同的自毁程序，一种用于半胱天冬酶依赖性细胞凋亡，另一种用于选择性轴突变性。
The selective degeneration of an axon, without the death of the parent neuron, can occur in response to injury, in a variety of metabolic, toxic, and inflammatory disorders, and during normal development. Recent evidence suggests that some forms of axon degeneration involve an active and regulated program of self-destruction rather than a passive “wasting away” and in this respect and others resemble apoptosis. Here we investigate whether selective axon degeneration depends on some of the molecular machinery that mediates apoptosis, namely, the caspase family of cysteine proteases. We focus on two models of selective axon degeneration: Wallerian degeneration of transected axons and localized axon degeneration induced by local deprivation of neurotrophin. We show that caspase-3 is not activated in the axon during either form of degeneration, although it is activated in the dying cell body of the same neurons. Moreover, caspase inhibitors do not inhibit or retard either form of axon degeneration, although they inhibit apoptosis of the same neurons. Finally, we cannot detect cleaved substrates of caspase-3 and its close relatives immunocytochemically or caspase activity biochemically in axons undergoing Wallerian degeneration. Our results suggest that a neuron contains at least two molecularly distinct self-destruction programs, one for caspase-dependent apoptosis and another for selective axon degeneration.
影响因子：
10.5
作者：
Woo, M;Hakem, R;Mak, TW
通讯作者：
Mak, TW
影响因子：
56.9
作者：
COWAN, WM;FAWCETT, JW;STANFIELD, BB
通讯作者：
STANFIELD, BB
DOI：
10.1016/s0169-328x(99)00032-7
发表时间：
1999-04-06
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Chaudhary, P;Ahmed, F;Sharma, SC
通讯作者：
Sharma, SC