Caspase-8: a key role in the pathogenesis of diabetic embryopathy.
Caspase-8: a key role in the pathogenesis of diabetic embryopathy.
复制标题
DOI：
10.1002/bdrb.20185
复制
发表时间：
2009-02
影响因子：
--
通讯作者：
Reece, E. Albert
中科院分区：
文献类型：
--
作者：
Zhao, Zhiyong;Yang, Peixin;Eckert, Richard L.;Reece, E. Albert
母体糖尿病导致胚胎神经管缺陷，这与神经上皮细胞凋亡增加有关。许多因素，包括效应半胱天冬酶，已被证明参与了这些事件，然而，关键的调节因子尚未确定，其潜在的机制仍有待解决。半胱天冬酶-8是一种起始半胱天冬酶，已被证明在糖尿病胚胎病中发生改变，表明其作为上游凋亡调节剂的作用。本研究以小鼠胚胎为模型系统，证明了半胱天冬酶-8是高血糖相关胚胎畸形产生所必需的。Caspase-8在发育中的神经管中表达。其活性，如增强的切割所证明的，通过高血糖而增加。这些变化与Bid活性裂解的形成增加有关。在高糖刺激的胚胎中抑制caspase-8活性可降低胚胎畸形率，这与神经管神经上皮细胞凋亡减少有关。caspase-8活性的抑制也降低了高血糖诱导的Bid活化和caspase-9裂解。这些数据表明，caspase-8可能通过调控Bid刺激的Ekon/caspase-9通路来控制糖尿病胚胎病相关的细胞凋亡。
Maternal diabetes causes neural tube defects in embryos which are associated with increased apoptosis in the neuroepithelium. Many factors, including effector caspases, have been shown to be involved in the events, however, the key regulators have not been identified and the underlying mechanisms remain to be addressed. Caspase-8, an initiator caspase, has been shown to be altered in diabetic embryopathy, suggesting a role as an upstream apoptotic regulator. Using mouse embryos as a model system, this study demonstrates that caspase-8 is required for the production of hyperglycemia-associated embryonic malformations. Caspase-8 was shown to be expressed in the developing neural tube. Its activity, as evidenced by enhanced cleavage, was increased by hyperglycemia. These changes were associated with increased formation of the active cleavage of Bid. Inhibition of caspase-8 activity in high glucose-challenged embryos reduced the rate of embryonic malformation and this was associated with decreased apoptosis in the neuroepithelium of the neural tube. Inhibition of caspase-8 activity also reduced hyperglycemia-induced Bid activation and caspase-9 cleavage. These data suggest that caspase-8 may control diabetic embryopathy-associated apoptosis via regulation of the Bid-stimulated mitochondrion/caspase-9 pathway.
登录
查看更多内容
影响因子：
9.8
作者：
Reece, EA;Wu, YK;Dhanasekaran, D
通讯作者：
Dhanasekaran, D
影响因子：
3.3
作者：
Gaereskog, Mattias;Cederberg, Jonas;Wentzel, Patti
通讯作者：
Wentzel, Patti
DOI：
10.1111/j.1600-0773.1998.tb01452.x
发表时间：
1998-09-01
期刊：
PHARMACOLOGY & TOXICOLOGY
影响因子：
--
作者：
Forsberg, H;Eriksson, UJ;Welsh, N
通讯作者：
Welsh, N
影响因子：
7.7
作者：
Fine, EL;Horal, M;Loeken, MR
通讯作者：
Loeken, MR
DOI：
10.1034/j.1600-0897.2002.01130.x
发表时间：
2002-10-01
影响因子：
3.6
作者：
Toder, V;Carp, H;Torchinsky, A
通讯作者：
Torchinsky, A