Abstract
Ghrelin functions as a neuroprotective agent and saves neurons from various insults include ischemic injury. However, it remains to be elucidated whether ghrelin protects neuronal cells against ischemic injury-induced excessive autophagy. Autophagy is required for the maintenance of neural stem cell homeostasis. However, regarding autophagic cell death, it is commonly assumed that excessive autophagy leads to self-elimination of mammalian cells. The purpose of this study was to investigate the potential neuroprotection effects of ghrelin from excessive autophagy in adult rat hippocampal neural stem cells (NSCs). Oxygen-Glucose Deprivation (OGD) strongly induces autophagy in adult rat hippocampal NSCs. Ghrelin treatment inhibited OGD-induced cell death of adult rat hippocampal NSCs assessed by cell-counting-kit-8 assay. Ghrelin also suppressed OGD-induced excessive autophagy activity. The protective effect of ghrelin was accompanied by an increased expression levels of Bcl-2, p-62 and decreased expression level of LC3-II, Beclin-1 by Western blot. Furthermore, ghrelin reduced autophagosome formation and number of GFP-LC3 transfected puncta. In conclusion, our data suggest that ghrelin protects adult rat hippocampal NSCs from excessive autophagy in experimental stroke (oxygen-glucose deprivation) model. Regulating autophagic activity may be a potential optimizing target for promoting adult rat hippocampal NSCs based therapy for stroke.
Keywords:
Excessive autophagy; Ghrelin; Hippocampus; Neuroprotection; Oxygen-glucose deprivation.
MeSH terms
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Adult Stem Cells / cytology
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Adult Stem Cells / metabolism
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Adult Stem Cells / pathology
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Adult Stem Cells / ultrastructure
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Animals
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Apoptosis
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Autophagy*
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Beclin-1 / antagonists & inhibitors
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Beclin-1 / metabolism
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Biomarkers / metabolism
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Cell Hypoxia
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Cell Proliferation
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Cells, Cultured
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Ghrelin / metabolism*
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Green Fluorescent Proteins / chemistry
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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Hippocampus / cytology
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Hippocampus / metabolism*
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Hippocampus / pathology
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Hippocampus / ultrastructure
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Hypoglycemia / metabolism
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Hypoglycemia / pathology
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Microscopy, Electron, Transmission
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Microtubule-Associated Proteins / antagonists & inhibitors
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Microtubule-Associated Proteins / chemistry
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Microtubule-Associated Proteins / genetics
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Microtubule-Associated Proteins / metabolism
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Nerve Tissue Proteins / agonists
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Nerve Tissue Proteins / antagonists & inhibitors
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Neural Stem Cells / cytology
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Neural Stem Cells / metabolism*
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Neural Stem Cells / pathology
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Neural Stem Cells / ultrastructure
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Neuroprotection*
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Proto-Oncogene Proteins c-bcl-2 / agonists*
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Rats, Inbred F344
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / metabolism
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Sequestosome-1 Protein / agonists*
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Sequestosome-1 Protein / metabolism
Substances
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Bcl2 protein, rat
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Beclin-1
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Becn1 protein, rat
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Biomarkers
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Ghrelin
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LC3 protein, rat
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Microtubule-Associated Proteins
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Nerve Tissue Proteins
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Proto-Oncogene Proteins c-bcl-2
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Recombinant Fusion Proteins
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Sequestosome-1 Protein
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Sqstm1 protein, rat
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Green Fluorescent Proteins