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Aagab acts as a novel regulator of NEDD4-1-mediated Pten nuclear translocation to promote neurological recovery following hypoxic-ischemic brain damage
- Source :
- Cell Death Differ
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- Hypoxic-ischemic encephalopathy (HIE) is a main cause of mortality and severe neurologic impairment in the perinatal and neonatal period. However, few satisfactory therapeutic strategies are available. Here, we reported that a rapid nuclear translocation of phosphatase and tensin homolog deleted on chromosome TEN (PTEN) is an essential step in hypoxic-ischemic brain damage (HIBD)- and oxygen-glucose deprivation (OGD)-induced neuronal injures both in vivo and in vitro. In addition, we found that OGD-induced nuclear translocation of PTEN is dependent on PTEN mono-ubiquitination at the lysine 13 residue (K13) that is mediated by neural precursor cell expressed developmentally downregulated protein 4-1 (NEDD4-1). Importantly, we for the first time identified α- and γ-adaptin binding protein (Aagab) as a novel NEDD4-1 regulator to regulate the level of NEDD4-1, subsequently mediating Pten nuclear translocation. Finally, we demonstrated that genetic upregulation of Aagab or application of Tat-K13 peptide (a short interference peptide that flanks K13 residue of PTEN) not only reduced Pten nuclear translocation, but also significantly alleviated the deficits of myodynamia, motor and spatial learning and memory in HIBD model rats. These results suggest that Aagab may serve as a regulator of NEDD4-1-mediated Pten nuclear translocation to promote functional recovery following HIBD in neonatal rats, and provide a new potential therapeutic target to guide the clinical treatment for HIE.
- Subjects :
- Male
0301 basic medicine
Nedd4 Ubiquitin Protein Ligases
Phosphatase
Regulator
NEDD4
Brain damage
Article
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
Pregnancy
Precursor cell
medicine
Animals
Humans
PTEN
Tensin
Molecular Biology
Brain Diseases
biology
PTEN Phosphohydrolase
Cell Biology
Rats
Up-Regulation
Cell biology
Adaptor Proteins, Vesicular Transport
Protein Transport
030104 developmental biology
030220 oncology & carcinogenesis
Hypoxia-Ischemia, Brain
biology.protein
Brain Damage, Chronic
Female
medicine.symptom
Signal Transduction
Subjects
Details
- ISSN :
- 14765403 and 13509047
- Volume :
- 28
- Database :
- OpenAIRE
- Journal :
- Cell Death & Differentiation
- Accession number :
- edsair.doi.dedup.....7603b8351a409a3b595fec4d5349fa98