Induced neural stem cells protect neuronal cells against apoptosis

Jin Hee Kim, Jang Bo Lee

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Neuronal cells are vulnerable to many stresses that can cause apoptosis. Reprogramming of fibroblasts into induced neural stem cells (iNSCs) is a potentially unlimited source of neurons. Discovering agents that can provide neuronal protection against these apoptotic stimuli is important for developing therapeutic strategies for various brain diseases. Material/Methods: We investigated the therapeutic effects of iNSCs against apoptosis activator II (AAII)-induced apoptosis of cortical neuronal cells. Apoptosis was confirmed by double immunocytochemistry with NeuN and 4’,6-diamidino-2-phenylindole using terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP-biotin nick-end labeling. We performed Western blot analyses for activated caspase-3, Bcl-2, phosphorylated Akt, and phosphorylated extracellular signal-regulated protein kinase (ERK). The level of vascular endothelial growth factor (VEGF) was analyzed using enzyme-linked immunosorbent assays (P<0.05). Results: Cortical neuronal cells cultured with iNSCs had fewer apoptotic cells than those cultured without iNSCs. We found that cells cultured with iNSCs had a significantly lower caspase-3 level and a significantly higher Bcl-2 level than cells cultured without iNSCs. Cells cultured with iNSCs had higher VEGF levels than cells cultured without iNSCs. The levels of phosphorylated Akt and phosphorylated ERK were significantly higher in cells  cultured with iNSCs than in cells cultured without iNSCs. Conclusions: Our findings suggest that iNSCs activate Akt and ERK, which are associated with the inhibition of neuronal apoptosis. Thus, treatment with iNSCs may help reduce neuronal loss in brain disease. Further studies aimed at proving this hypothesis might help establish therapeutic agents that can prevent neuronal cell death and help cure neurodegenerative diseases.

Original languageEnglish
Pages (from-to)2759-2766
Number of pages8
JournalMedical Science Monitor
Volume20
DOIs
Publication statusPublished - 2014 Dec 22

Fingerprint

Neural Stem Cells
Apoptosis
Cultured Cells
Brain Diseases
Caspase 3
Vascular Endothelial Growth Factor A
Digoxigenin
DNA Nucleotidylexotransferase
Extracellular Signal-Regulated MAP Kinases
Therapeutic Uses
Biotin
Neurodegenerative Diseases
Protein Kinases
Cell Death
Therapeutics
Fibroblasts
Western Blotting
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry

Keywords

  • Apoptosis
  • Cerebral cortex
  • Stem cell research

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Induced neural stem cells protect neuronal cells against apoptosis. / Kim, Jin Hee; Lee, Jang Bo.

In: Medical Science Monitor, Vol. 20, 22.12.2014, p. 2759-2766.

Research output: Contribution to journalArticle

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AB - Background: Neuronal cells are vulnerable to many stresses that can cause apoptosis. Reprogramming of fibroblasts into induced neural stem cells (iNSCs) is a potentially unlimited source of neurons. Discovering agents that can provide neuronal protection against these apoptotic stimuli is important for developing therapeutic strategies for various brain diseases. Material/Methods: We investigated the therapeutic effects of iNSCs against apoptosis activator II (AAII)-induced apoptosis of cortical neuronal cells. Apoptosis was confirmed by double immunocytochemistry with NeuN and 4’,6-diamidino-2-phenylindole using terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP-biotin nick-end labeling. We performed Western blot analyses for activated caspase-3, Bcl-2, phosphorylated Akt, and phosphorylated extracellular signal-regulated protein kinase (ERK). The level of vascular endothelial growth factor (VEGF) was analyzed using enzyme-linked immunosorbent assays (P<0.05). Results: Cortical neuronal cells cultured with iNSCs had fewer apoptotic cells than those cultured without iNSCs. We found that cells cultured with iNSCs had a significantly lower caspase-3 level and a significantly higher Bcl-2 level than cells cultured without iNSCs. Cells cultured with iNSCs had higher VEGF levels than cells cultured without iNSCs. The levels of phosphorylated Akt and phosphorylated ERK were significantly higher in cells  cultured with iNSCs than in cells cultured without iNSCs. Conclusions: Our findings suggest that iNSCs activate Akt and ERK, which are associated with the inhibition of neuronal apoptosis. Thus, treatment with iNSCs may help reduce neuronal loss in brain disease. Further studies aimed at proving this hypothesis might help establish therapeutic agents that can prevent neuronal cell death and help cure neurodegenerative diseases.

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