Agmatine enhances neurogenesis by increasing ERK1/2 expression, and suppresses astrogenesis by decreasing BMP 2,4 and SMAD 1,5,8 expression in subventricular zone neural stem cells

Ho Won Song, Bokara Kiran Kumar, Sa Hyun Kim, Yong Heui Jeon, Yoon Azalea Lee, Won Teak Lee, Kyung Ah Park, Jongeun Lee

Research output: Contribution to journalArticle

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Abstract

Aim: Our study aimed to demonstrate whether agmatine (Ag) could regulate proliferation and cell fate determination of subventricular zone neural stem cells (SVZ NSCs). Main methods: SVZ NSCs were grown in the presence of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) (20 ng/ml) until 4 days in vitro (DIV) and later the culture medium was replaced without EGF and bFGF until 11 DIV in the absence (EGF/bFGF +/- /Ag - ) or presence of agmatine (EGF/bFGF +/- /Ag + ). Another set SVZ NSCs were maintained with EGF and bFGF until 11 DIV without (EGF/bFGF +/+ /Ag - ) or with agmatine treatment (EGF/bFGF +/+ /Ag + ). Agmatine's effect on proliferation and cell death (H and PI staining and Caspase-3 immunostaining) was examined at DIV 4 and 11. Agmatine's (100 μM) effect on cell fate determination was confirmed by immunostaining and Western blot at 11 DIV. Key findings: Agmatine treatment reduced the neurosphere size and total cell count number dose-dependently in all the experimental groups both at DIV 4 and11. Immunoblotting and staining results showed that agmatine increased the Tuj1 and Microtubule-associated protein 2 (MAP2) and decreased the Glial fibrillary acidic protein (GFAP) with no change in the Oligo2 protein expressions. This neurogenesis effect of agmatine seems to have a relation with Extracellular-signal-regulated kinases (ERK1/2) activation and anti-astrogenesis effect is thought to be related with the suppression of Bone morphogenetic proteins (BMP) 2,4 and contraction of Sma and Mad (SMAD) 1,5,8 protein expression. Significance: This model could be an invaluable tool to study whether agmatine treated SVZ NSC transplantation to the central nervous system (CNS) injury could trigger neurogenesis and decrypt the full range of molecular events involved during neurogenesis in vivo as evidenced in vitro.

Original languageEnglish
Pages (from-to)439-449
Number of pages11
JournalLife Sciences
Volume89
Issue number13-14
DOIs
Publication statusPublished - 2011 Sep 26

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Agmatine
Bone Morphogenetic Protein 4
Bone Morphogenetic Protein 2
Neural Stem Cells
Lateral Ventricles
Neurogenesis
Stem cells
Fibroblast Growth Factor 2
Epidermal Growth Factor
Cell Count
Staining and Labeling
Nervous System Trauma
Microtubule-Associated Proteins
Mitogen-Activated Protein Kinase 1
Glial Fibrillary Acidic Protein
Extracellular Signal-Regulated MAP Kinases
Neurology
Stem Cell Transplantation
Cell death
In Vitro Techniques

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Song, Ho Won ; Kumar, Bokara Kiran ; Kim, Sa Hyun ; Jeon, Yong Heui ; Lee, Yoon Azalea ; Lee, Won Teak ; Park, Kyung Ah ; Lee, Jongeun. / Agmatine enhances neurogenesis by increasing ERK1/2 expression, and suppresses astrogenesis by decreasing BMP 2,4 and SMAD 1,5,8 expression in subventricular zone neural stem cells. In: Life Sciences. 2011 ; Vol. 89, No. 13-14. pp. 439-449.
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abstract = "Aim: Our study aimed to demonstrate whether agmatine (Ag) could regulate proliferation and cell fate determination of subventricular zone neural stem cells (SVZ NSCs). Main methods: SVZ NSCs were grown in the presence of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) (20 ng/ml) until 4 days in vitro (DIV) and later the culture medium was replaced without EGF and bFGF until 11 DIV in the absence (EGF/bFGF +/- /Ag - ) or presence of agmatine (EGF/bFGF +/- /Ag + ). Another set SVZ NSCs were maintained with EGF and bFGF until 11 DIV without (EGF/bFGF +/+ /Ag - ) or with agmatine treatment (EGF/bFGF +/+ /Ag + ). Agmatine's effect on proliferation and cell death (H and PI staining and Caspase-3 immunostaining) was examined at DIV 4 and 11. Agmatine's (100 μM) effect on cell fate determination was confirmed by immunostaining and Western blot at 11 DIV. Key findings: Agmatine treatment reduced the neurosphere size and total cell count number dose-dependently in all the experimental groups both at DIV 4 and11. Immunoblotting and staining results showed that agmatine increased the Tuj1 and Microtubule-associated protein 2 (MAP2) and decreased the Glial fibrillary acidic protein (GFAP) with no change in the Oligo2 protein expressions. This neurogenesis effect of agmatine seems to have a relation with Extracellular-signal-regulated kinases (ERK1/2) activation and anti-astrogenesis effect is thought to be related with the suppression of Bone morphogenetic proteins (BMP) 2,4 and contraction of Sma and Mad (SMAD) 1,5,8 protein expression. Significance: This model could be an invaluable tool to study whether agmatine treated SVZ NSC transplantation to the central nervous system (CNS) injury could trigger neurogenesis and decrypt the full range of molecular events involved during neurogenesis in vivo as evidenced in vitro.",
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Agmatine enhances neurogenesis by increasing ERK1/2 expression, and suppresses astrogenesis by decreasing BMP 2,4 and SMAD 1,5,8 expression in subventricular zone neural stem cells. / Song, Ho Won; Kumar, Bokara Kiran; Kim, Sa Hyun; Jeon, Yong Heui; Lee, Yoon Azalea; Lee, Won Teak; Park, Kyung Ah; Lee, Jongeun.

In: Life Sciences, Vol. 89, No. 13-14, 26.09.2011, p. 439-449.

Research output: Contribution to journalArticle

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T1 - Agmatine enhances neurogenesis by increasing ERK1/2 expression, and suppresses astrogenesis by decreasing BMP 2,4 and SMAD 1,5,8 expression in subventricular zone neural stem cells

AU - Song, Ho Won

AU - Kumar, Bokara Kiran

AU - Kim, Sa Hyun

AU - Jeon, Yong Heui

AU - Lee, Yoon Azalea

AU - Lee, Won Teak

AU - Park, Kyung Ah

AU - Lee, Jongeun

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