c-Abl is involved in high glucose-induced apoptosis in embryonic E12.5 cortical neural progenitor cells from the mouse brain
c-Abl is involved in high glucose-induced apoptosis in embryonic E12.5 cortical neural progenitor cells from the mouse brain
复制标题
c-Abl 参与高葡萄糖诱导的小鼠大脑胚胎 E12.5 皮质神经祖细胞凋亡
DOI：
10.1111/j.1471-4159.2008.05533.x
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发表时间：
2008-08-01
影响因子：
4.7
通讯作者：
Hao, Ai-jun
中科院分区：
文献类型：
--
作者：
Jia, De-yong;Du, Zhan-hui;Hao, Ai-jun
糖尿病诱导的胚胎神经管畸形中，高血糖导致神经祖细胞（NPC）直接凋亡。然而，对潜在的机制知之甚少。本研究的目的是探讨可能参与NPCs凋亡的特异性细胞蛋白及其调控氧化应激诱导的NPCs凋亡的机制。我们的研究结果表明，高糖诱导的体外培养的NPC中c-Abl的表达上调。c-Abl的增高主要位于核内。高糖还诱导NPC中核p53蛋白水平和p53-c-Abl复合物的增加。给予活性氧清除剂可降低c-Abl、p53蛋白水平和NPCs凋亡。抑制c-Abl可降低高糖诱导的NPC凋亡和p53核蛋白水平。这些结果表明，c-Abl参与了活性氧激活的NPC凋亡途径。抑制c-Abl可能通过调节NPC凋亡机制来保护NPC免受高糖诱导的损伤。
Hyperglycemia causes direct apoptosis of neural progenitor cells (NPCs) in diabetic-induced neural tube defects in embryos. However, the underlying mechanisms are poorly understood. The present study is aimed to investigate the specific cellular proteins that may be involved in NPCs apoptosis as well as mechanisms by which the proteins regulate the oxidative stress-induced NPCs apoptosis. Our present results have shown that the expression of c-Abl was up-regulated in NPCs exposed to high glucose in vitro. The increased c-Abl was localized mainly in the nucleus. High glucose also induced an increase in nuclear p53 protein levels and the p53-c-Abl complex in NPCs. Administration of reactive oxygen species scavengers decreased the protein level of c-Abl, p53 and NPCs apoptosis. Inhibition of c-Abl reduced NPCs apoptosis and the nuclear protein level of p53 in response to high glucose. These results demonstrate that c-Abl is involved in the reactive oxygen species-activated apoptotic pathways in NPCs apoptosis. Inhibition of c-Abl may protect NPCs against insults induced by high glucose via the modulation of NPCs apoptotic machinery.