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NQDI-1, an inhibitor of ASK1 attenuates acute perinatal hypoxic-ischemic cerebral injury by modulating cell death

  • Authors:
    • Hu Hao
    • Sitao Li
    • Hui Tang
    • Bingqing Liu
    • Yao Cai
    • Congcong Shi
    • Xin Xiao
  • View Affiliations / Copyright

    Affiliations: Department of Pediatrics, The Sixth Affiliated Hospital of Sun Yat‑Sen University, Guangzhou, Guangdong 510655, P.R. China, Central Laboratory, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510630 P.R. China
    Copyright: © Hao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4585-4592
    |
    Published online on: April 13, 2016
       https://doi.org/10.3892/mmr.2016.5123
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Abstract

Apoptosis signal-regulating kinase 1 (ASK1) is a ubiquitously expressed protein kinase, which regulates cell fate in numerous injury conditions. Therefore, ASK1 may be a promising novel therapeutic target for injury. However, the expression and distribution of ASK1 in the perinatal brain following hypoxia-ischemia (HI) remains to be elucidated. In the present study, western blotting and immunofluorescence were used to determine the expression and distribution of ASK1 and any associated downstream targets in the perinatal rat brain following HI. NQDI‑1, a specific inhibitor of ASK1 was intracerebroventricularly injected following neonatal rats brain insult for neuroprotection. The results revealed an increased expression of ASK1 and this expression was localized to the neurons and astrocytes, compared with the sham controls. Additionally, it was demonstrated that the ASK1/ c‑Jun N‑terminal kinases (JNK) pathway was involved in the brain damage following HI in neonatal rats. Notably, NQDI‑1 significantly inhibited the in vivo expression levels of ASK1, phosphorylated (p‑)JNK, p‑c‑Jun, p53 and caspase 3. Reduced acute hypoxic‑ischemic cerebral injury and cell apoptosis was observed following the injection of NQDI‑1. Collectively, NQDI-1 attenuated acute perinatal hypoxic‑ischemic cerebral injury by inhibiting the expression of ASK1 and cell apoptosis. This may be a promising novel neuroprotective inhibitor for perinatal cerebra injury.
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Copy and paste a formatted citation
Spandidos Publications style
Hao H, Li S, Tang H, Liu B, Cai Y, Shi C and Xiao X: NQDI-1, an inhibitor of ASK1 attenuates acute perinatal hypoxic-ischemic cerebral injury by modulating cell death. Mol Med Rep 13: 4585-4592, 2016.
APA
Hao, H., Li, S., Tang, H., Liu, B., Cai, Y., Shi, C., & Xiao, X. (2016). NQDI-1, an inhibitor of ASK1 attenuates acute perinatal hypoxic-ischemic cerebral injury by modulating cell death. Molecular Medicine Reports, 13, 4585-4592. https://doi.org/10.3892/mmr.2016.5123
MLA
Hao, H., Li, S., Tang, H., Liu, B., Cai, Y., Shi, C., Xiao, X."NQDI-1, an inhibitor of ASK1 attenuates acute perinatal hypoxic-ischemic cerebral injury by modulating cell death". Molecular Medicine Reports 13.6 (2016): 4585-4592.
Chicago
Hao, H., Li, S., Tang, H., Liu, B., Cai, Y., Shi, C., Xiao, X."NQDI-1, an inhibitor of ASK1 attenuates acute perinatal hypoxic-ischemic cerebral injury by modulating cell death". Molecular Medicine Reports 13, no. 6 (2016): 4585-4592. https://doi.org/10.3892/mmr.2016.5123
Copy and paste a formatted citation
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Spandidos Publications style
Hao H, Li S, Tang H, Liu B, Cai Y, Shi C and Xiao X: NQDI-1, an inhibitor of ASK1 attenuates acute perinatal hypoxic-ischemic cerebral injury by modulating cell death. Mol Med Rep 13: 4585-4592, 2016.
APA
Hao, H., Li, S., Tang, H., Liu, B., Cai, Y., Shi, C., & Xiao, X. (2016). NQDI-1, an inhibitor of ASK1 attenuates acute perinatal hypoxic-ischemic cerebral injury by modulating cell death. Molecular Medicine Reports, 13, 4585-4592. https://doi.org/10.3892/mmr.2016.5123
MLA
Hao, H., Li, S., Tang, H., Liu, B., Cai, Y., Shi, C., Xiao, X."NQDI-1, an inhibitor of ASK1 attenuates acute perinatal hypoxic-ischemic cerebral injury by modulating cell death". Molecular Medicine Reports 13.6 (2016): 4585-4592.
Chicago
Hao, H., Li, S., Tang, H., Liu, B., Cai, Y., Shi, C., Xiao, X."NQDI-1, an inhibitor of ASK1 attenuates acute perinatal hypoxic-ischemic cerebral injury by modulating cell death". Molecular Medicine Reports 13, no. 6 (2016): 4585-4592. https://doi.org/10.3892/mmr.2016.5123
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