MST4 Kinase Inhibitor Hesperadin Attenuates Autophagy and Behavioral Disorder via the MST4/AKT Pathway in Intracerebral Hemorrhage Mice

  • Behav Neurol. 2020 Feb 3;2020:2476861. doi: 10.1155/2020/2476861.
Xiaodong Wu  1  2 ,  Jinting Wu  3 ,  Wenjie Hu  4 ,  Qinghua Wang  4 ,  Hairong Liu  5 ,  Zhaohu Chu  4 ,  Kun Lv  1 ,  Yang Xu  1  4
Affiliations
  • 1. Key Laboratory of Noncoding RNA Transformation Research of Anhui Higher Education Institution (Wannan Medical College), The First Affiliated Hospital of Wannan Medical College, Wuhu, 241000 Anhui, China.
  • 2. Department of Neurology, The Second Affiliated Hospital of Wannan Medical College, Wuhu, 241000 Anhui, China.
  • 3. The Second Affiliated Hospital of Wannan Medical College, Wuhu, 241000 Anhui, China.
  • 4. Department of Neurology, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241000 Anhui, China.
  • 5. Department of Public Administration, Wannan Medical College, Wuhu, 241000 Anhui, China.
PMID: 32089749 DOI: 10.1155/2020/2476861
Abstract

Background: The aim of this study was to explore the role of hesperadin in intracerebral hemorrhage (ICH) mice, with the involvement of the mammalian ste20-like kinase 4 (MST4)/Akt signaling pathway.

Methods: All mice were divided into four groups: sham group, sham+hesperidin group, ICH group, and ICH+hesperadin group. The effects of hesperadin were assessed on the basis of brain edema and neurobehavioral function. Furthermore, we observed MST4, Akt, phosphorylation of Akt (pAKT), and microtubule-associated protein light chain 3 (LC3) by western blotting. Protein localization of MST4 and LC3 was determined by immunofluorescence.

Results: The expression of MST4 was upregulated at 12 h and 24 h after ICH. Brain edema was significantly decreased and neurological function was improved in the hesperadin treatment group compared to the ICH group (P < 0.05). Hesperadin decreases the expressions of MST and increases pAKT after ICH. Autophagy significantly increased in the ICH group, while hesperadin reduced this increase.

Conclusion: Hesperadin provides neuroprotection against ICH by inhibiting the MST4/Akt signaling pathway.

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