NG25, an inhibitor of transforming growth factor‑β‑activated kinase 1, ameliorates neuronal apoptosis in neonatal hypoxic‑ischemic rats.
NG25, an inhibitor of transforming growth factor‑β‑activated kinase 1, ameliorates neuronal apoptosis in neonatal hypoxic‑ischemic rats.
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NG25是转化生长因子 - 激活激活激酶1的抑制剂，可改善新生儿低氧缺血性渗透性大鼠的神经元凋亡。
DOI：
10.3892/mmr.2017.8024
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发表时间：
2018-01
影响因子：
3.4
通讯作者：
Ji Q
中科院分区：
文献类型：
--
作者：
Wang H;Chen Z;Li Y;Ji Q
转化生长因子-β激活的蛋白1(Tak1)被转化生长因子-β激活，在多种疾病中起着细胞死亡的中枢调节作用。然而，TAK1在缺氧缺血(HI)后新生脑组织中的表达和功能仍不清楚。本研究采用免疫印迹和免疫荧光技术检测了TAK1在围产期HI模型大鼠大脑皮质中的表达和分布。此外，在损伤新生大鼠大脑之前，通过脑室注射TAK1的特异性抑制剂NG25来保护神经。Western blotting和免疫荧光双标记法显示，与假手术组相比，磷酸化的TAK1表达水平增加，并且定位于神经元和星形胶质细胞。进一步研究表明，损伤前注射NG25可显著抑制TAK1/c-jun氨基末端激酶活性，并通过抑制细胞凋亡而显著改善围产期大鼠急性缺氧缺血性脑损伤。因此，NG25通过抑制TAK1的表达和细胞凋亡而改善新生HI大鼠神经细胞的凋亡。此外，NG25可能成为治疗围产期脑损伤的一种新的神经保护抑制剂。
Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) was found to be activated by TGF-β and acts as a central regulator of cell death in various types of disease. However, the expression and function of TAK1 in the neonatal brain following hypoxia-ischemia (HI) remains unclear. In the present study, western blotting and immunofluorescence were employed to determine the expression and distribution of TAK1 in the brain cortex of a perinatal HI rat model. In addition, the specific inhibitor of TAK1, NG25 was administered via intracerebroventricular injection, prior to insult of the neonatal rat brains, for neuroprotection. Western blotting and double immunofluorescence indicated that an increased expression level of phosphorylated-TAK1 was observed, and was localized with neurons and astrocytes, compared with the sham group. Further study demonstrated that injection of NG25 prior to insult significantly inhibited TAK1/c-Jun N-terminal kinases activity and dramatically ameliorated acute hypoxic-ischemic cerebral injury by inhibiting cell apoptosis in perinatal rats. Thus, NG25 ameliorates neuronal apoptosis in neonatal HI rats by inhibiting TAK1 expression and cell apoptosis. In addition, NG25 may serve as a promising novel neuroprotective inhibitor for perinatal cerebral injury.
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影响因子：
1.9
作者：
Hagberg H;Mallard C;Rousset CI;Xiaoyang Wang
通讯作者：
Xiaoyang Wang
影响因子：
15.1
作者：
Nijboer, Cora H.;van der Kooij, Michael A.;Kavelaars, Annemieke
通讯作者：
Kavelaars, Annemieke
影响因子：
4.6
作者：
Wang Z;Zhang H;Shi M;Yu Y;Wang H;Cao WM;Zhao Y;Zhang H
通讯作者：
Zhang H
影响因子：
3.6
作者：
Gu Y;Zhang Y;Bi Y;Liu J;Tan B;Gong M;Li T;Chen J
通讯作者：
Chen J
DOI：
10.1136/adc.2004.067520
发表时间：
2005-09-01
影响因子：
4.4
作者：
Marlow, N;Rose, AS;Draper, ES
通讯作者：
Draper, ES