NG25, an inhibitor of transforming growth factor‑β‑activated kinase 1, ameliorates neuronal apoptosis in neonatal hypoxic‑ischemic rats

Wang,Hua; Chen,Zhong; Li,Yu; Ji,Qiaoyun

doi:10.3892/mmr.2017.8024

NG25, an inhibitor of transforming growth factor‑β‑activated kinase 1, ameliorates neuronal apoptosis in neonatal hypoxic‑ischemic rats

Authors:
- Hua Wang
- Zhong Chen
- Yu Li
- Qiaoyun Ji
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Affiliations: Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China, Department of Ophthalmology, Fourth Affiliated Hospital of Sichuan University, Sichuan University, Chengdu, Sichuan 610041, P.R. China
Published online on: November 10, 2017 https://doi.org/10.3892/mmr.2017.8024
Pages: 1710-1716
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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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