Protein kinase Cβ2 inhibition reduces hyperglycemia-induced neural tube defects through suppression of a caspase 8-triggered apoptotic pathway.
Protein kinase Cβ2 inhibition reduces hyperglycemia-induced neural tube defects through suppression of a caspase 8-triggered apoptotic pathway.
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DOI：
10.1016/j.ajog.2011.01.013
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发表时间：
2011-03
影响因子：
9.8
通讯作者：
Reece EA
中科院分区：
文献类型：
--
作者：
Cao Y;Zhao Z;Eckert RL;Reece EA
糖尿病母亲的婴儿神经管缺陷（NTDs）与早期胚胎发育过程中神经上皮中蛋白激酶C β2（PKCβ2）活性增加和程序性细胞死亡（凋亡）有关。糖尿病胚胎病中的细胞凋亡由caspase 8触发，caspase 8是一种启动caspase，其激活涉及caspase和Bcl-2家族成员（如caspase 3和Bid）以及细胞色素C的级联分子事件。PKCβ2是否调节caspase 8诱导的细胞凋亡仍有待研究。将胚胎（E）第8.5天（E8.5）的小鼠胚胎在高浓度葡萄糖（22 mM）中培养，并用PKCβ2抑制剂（50 nM）处理48小时。观察胚胎发育和神经管畸形。TUNEL法检测细胞凋亡。用Western blot分析评估凋亡因子活化的变化。抑制PKCβ2可显著降低NTD率至与正常血糖对照组相似的水平（8.3 mM）。半胱天冬酶8的激活，如切割形式所示，显著低于高血糖组（p<0.05），与正常血糖对照组相似。对于细胞色素C、半胱天冬酶3和Bid也观察到类似的结果（p<0.05）。PKCβ2通过影响caspase 8调节的凋亡途径介导母体高血糖对糖尿病胚胎病中胚胎NTDs的影响
Neural tube defects (NTDs) in infants of diabetic mothers are associated with increased protein kinase C β2 (PKCβ2) activity and programmed cell death (apoptosis) in the neuroepithelium during early embryogenesis. Apoptosis in diabetic embryopathy is triggered by caspase8, an initiator caspase which activates a cascade of molecular events involving members of the caspase and Bcl-2 families, such as caspase3 and Bid, as well as Cytochrome C. Whether PKCβ2 regulates caspase8-induced apoptosis remains to be addressed. Mouse embryos at embryonic (E) day 8.5 (E8.5) were cultured in a high concentration of glucose (22 mM) and treated with PKCβ2 inhibitor (50 nM) for 48 hours. The embryonic development and NTDs were examined. Apoptosis was assessed using TUNEL assay. Changes in activation of apoptotic factors were assessed using Western blot assay. Inhibition of PKCβ2 significantly reduced NTD rate to the similar level as in euglycemic control (8.3 mM). Activation of caspase8, as indicated with a cleaved form, was significantly lower than that in the hyperglycemic group (p<0.05), and similar to that in euglycemic control. Similar results were also observed for Cytochrome C, caspase3, and Bid (p<0.05). PKCβ2 mediates the effect of maternal hyperglycemia on embryonic NTDs in diabetic embryopathy by influencing a caspase8-regulated apoptotic pathway.
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影响因子：
1.8
作者：
Reece, E. Albert
通讯作者：
Reece, E. Albert
影响因子：
20.1
作者：
Geraldes P;King GL
通讯作者：
King GL
DOI：
10.1083/jcb.119.3.493
发表时间：
1992-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gavrieli Y;Sherman Y;Ben-Sasson SA
通讯作者：
Ben-Sasson SA
影响因子：
4.7
作者：
Niizuma K;Endo H;Chan PH
通讯作者：
Chan PH
影响因子：
4.8
作者：
Godbout, JP;Pesavento, J;Freund, GG
通讯作者：
Freund, GG