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Downregulation of lncRNA GAS5 prevents mitochondrial apoptosis and hypoxic-ischemic brain damage in neonatal rats through the microRNA-128-3p/Bax/Akt/GSK-3β axis

Wang, Li, Zhang, Zhe, Wang, Haibin·2021·NeuroReport
DOI 10.1097/wnr.0000000000001730
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Abstract

Objective: Hypoxic/ischemic brain damage (HIBD) results in increased neonatal mortality and serious neurologic morbidity. Long noncoding RNAs (lncRNAs) are shown as essential modulators of various neurological diseases. Here, we determined the mechanisms of lncRNA GAS5 in mitochondrial apoptosis in HIBD rats. Methods: The HIBD neonatal rat model was established and treated with shRNA-GAS5 or antagomir miR-128-3p. The morphological changes and apoptosis rate were observed by histological staining. Expressions of GAS5, miR-128-3p, and Bax mRNA in brain tissues of HIBD neonatal rats were determined. The binding relationships between GAS5 and miR-128-3p, and miR-128-3p and Bax were confirmed by dual-luciferase assay. Subsequently, the mitochondrial membrane potential and apoptosis-related factors in brain tissues of HIBD neonatal rats were detected. Western blot analysis was performed to detect the expression of Akt/GSK3β pathway-associated proteins. Results: The neurons in the brain tissue of HIBD neonatal rats decreased with disordered arrangement, and showed vacuolization and nuclear pyknosis, obvious brain damage, increased neuronal apoptosis, and enhanced mitochondrial apoptotic pathway. Downregulated miR-128-3p and upregulated GAS5 and Bax mRNA were found in HIBD neonatal rats. There were binding relationships between GAS5 and miR-128-3p, and miR-128-3p and Bax mRNA. Inhibition of lncRNA GAS5 in HIBD neonatal rats suppressed mitochondrial apoptosis. miR-128-3p knockdown annulled the inhibitory effect of inhibiting lncRNA GAS5 on mitochondrial apoptosis. Silencing GAS5 increased the phosphorylation levels of Akt and GSK3β. Conclusion: Downregulation of lncRNA GAS5 prevents mitochondrial apoptosis in neonatal HIBD rats by regulating the miR-128-3p/Bax/Akt/GSK-3β axis.

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Metadata

Authors
Wang, L., Zhang, Z., & Wang, H.
Affiliations
  • Department of Emergency Medicine, The Second Affiliated Hospital, Zhejiang University School of Medicine
  • Department of Emergency Medicine, Yuhang Branch of the Second Affiliated Hospital of Zhejiang University School of Medicine, The First People’s Hospital of Yuhang District
  • Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Translational Medicine Research Center, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
Venue
NeuroReport
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2021-10-22
Volume
32
Issue
17
Pages
1395-1402
ISSN
0959-4965
DOI
10.1097/wnr.0000000000001730
Cited by
18
References
2
Language
en

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