Neuronal differentiation of embryonic midbrain cells by upregulation of peroxisome proliferator-activated receptor-gamma via the JNK-dependent pathway

Ki Sook Park; Rhee Da Lee; Sun Kyung Kang; Soon Young Han; Kui Lae Park; Ki Hwa Yang; Youn Sook Song; Hye Ji Park; Yoot Mo Lee; Yeo Pyo Yun; Ki Wan Oh; Dae Joong Kim; Young Won Yun; Se Jin Hwang; Sung Eun Lee; Jin Tae Hong

doi:10.1016/j.yexcr.2004.03.034

Neuronal differentiation of embryonic midbrain cells by upregulation of peroxisome proliferator-activated receptor-gamma via the JNK-dependent pathway

Ki Sook Park, Rhee Da Lee, Sun Kyung Kang, Soon Young Han, Kui Lae Park, Ki Hwa Yang, Youn Sook Song, Hye Ji Park, Yoot Mo Lee, Yeo Pyo Yun, Ki Wan Oh, Dae Joong Kim, Young Won Yun, Se Jin Hwang, Sung Eun Lee, Jin Tae Hong

School of Applied Bioscience

Research output: Contribution to journal › Article › peer-review

95 Scopus citations

Abstract

Our previous study showed that the peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonist 15-deoxy-PGJ₂ has the promoting ability to differentiate neuronal PC12 cells. To expand our study, the effect of 15-deoxy-PGJ₂ on the differentiation of embryonic midbrain cells into dopaminergic neuronal cells was investigated in this study. The relationship between cell differentiation with activation of PPAR-γ and the possible signal pathway were also investigated. 15-Deoxy-PGJ₂ increased neurite extension, a typical characteristic of the differentiation of embryonic midbrain cells isolated from 12-day rat embryos in a dose-dependent manner. The expression of differentiation markers, neurofilament, tyrosine hydroxylase, and nestin, was also increased by the treatment of 15-deoxy-PGJ₂. Consistent with the increasing effect on cell differentiation, 15-deoxy-PGJ₂ increased the expression and transcriptional activity of PPAR-γ in cultured embryonic midbrain cells. In addition, the expression of PPAR-γ and NeuN in the differentiated neuron of fetus (17 days) and adult rat brain was co-localized. Furthermore, treatment of PPAR-γ antagonist bisphenol A diglycidyl ether blocked 15-deoxy-PGJ₂-induced neuronal differentiation of embryonic midbrain cells and expression of PPAR-γ. To elucidate the possible signal pathway, the activation of mitogenic-activated protein (MAP) kinase family was determined. 15-Deoxy-PGJ₂ (0.5 μM) increased activation of Jun N-terminal kinase (JNK) and p38 kinase but not extra-signal response kinase (ERK). In addition, NGF (50 ng/ml) further increased the 15-deoxy-PGJ ₂-induced JNK activation. Moreover, pretreatment of specific inhibitor of JNK SP600125 blocked the 15-deoxy-PGJ₂-induced JNK activation. This inhibition correlated well with the inhibition of neurite extension and expression of PPAR-γ induced by 15-deoxy-PGJ₂. The present results therefore indicate that 15-deoxy-PGJ₂ stimulates differentiation of embryonic midbrain cells into dopaminergic neuronal cells, and its effect may be PPAR-γ and JNK signal pathway dependent.

Original language	English
Pages (from-to)	424-433
Number of pages	10
Journal	Experimental Cell Research
Volume	297
Issue number	2
DOIs	https://doi.org/10.1016/j.yexcr.2004.03.034
State	Published - 15 Jul 2004

Keywords

15-Deoxy-PGJ
Differentiation
Embryonic midbrain cell
JNK
PPAR-γ

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10.1016/j.yexcr.2004.03.034

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Park, K. S., Lee, R. D., Kang, S. K., Han, S. Y., Park, K. L., Yang, K. H., Song, Y. S., Park, H. J., Lee, Y. M., Yun, Y. P., Oh, K. W., Kim, D. J., Yun, Y. W., Hwang, S. J., Lee, S. E., & Hong, J. T. (2004). Neuronal differentiation of embryonic midbrain cells by upregulation of peroxisome proliferator-activated receptor-gamma via the JNK-dependent pathway. Experimental Cell Research, 297(2), 424-433. https://doi.org/10.1016/j.yexcr.2004.03.034

@article{3318c31729464ed79ef25f029d75f233,

title = "Neuronal differentiation of embryonic midbrain cells by upregulation of peroxisome proliferator-activated receptor-gamma via the JNK-dependent pathway",

abstract = "Our previous study showed that the peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonist 15-deoxy-PGJ2 has the promoting ability to differentiate neuronal PC12 cells. To expand our study, the effect of 15-deoxy-PGJ2 on the differentiation of embryonic midbrain cells into dopaminergic neuronal cells was investigated in this study. The relationship between cell differentiation with activation of PPAR-γ and the possible signal pathway were also investigated. 15-Deoxy-PGJ2 increased neurite extension, a typical characteristic of the differentiation of embryonic midbrain cells isolated from 12-day rat embryos in a dose-dependent manner. The expression of differentiation markers, neurofilament, tyrosine hydroxylase, and nestin, was also increased by the treatment of 15-deoxy-PGJ2. Consistent with the increasing effect on cell differentiation, 15-deoxy-PGJ2 increased the expression and transcriptional activity of PPAR-γ in cultured embryonic midbrain cells. In addition, the expression of PPAR-γ and NeuN in the differentiated neuron of fetus (17 days) and adult rat brain was co-localized. Furthermore, treatment of PPAR-γ antagonist bisphenol A diglycidyl ether blocked 15-deoxy-PGJ2-induced neuronal differentiation of embryonic midbrain cells and expression of PPAR-γ. To elucidate the possible signal pathway, the activation of mitogenic-activated protein (MAP) kinase family was determined. 15-Deoxy-PGJ2 (0.5 μM) increased activation of Jun N-terminal kinase (JNK) and p38 kinase but not extra-signal response kinase (ERK). In addition, NGF (50 ng/ml) further increased the 15-deoxy-PGJ 2-induced JNK activation. Moreover, pretreatment of specific inhibitor of JNK SP600125 blocked the 15-deoxy-PGJ2-induced JNK activation. This inhibition correlated well with the inhibition of neurite extension and expression of PPAR-γ induced by 15-deoxy-PGJ2. The present results therefore indicate that 15-deoxy-PGJ2 stimulates differentiation of embryonic midbrain cells into dopaminergic neuronal cells, and its effect may be PPAR-γ and JNK signal pathway dependent.",

keywords = "15-Deoxy-PGJ, Differentiation, Embryonic midbrain cell, JNK, PPAR-γ",

author = "Park, {Ki Sook} and Lee, {Rhee Da} and Kang, {Sun Kyung} and Han, {Soon Young} and Park, {Kui Lae} and Yang, {Ki Hwa} and Song, {Youn Sook} and Park, {Hye Ji} and Lee, {Yoot Mo} and Yun, {Yeo Pyo} and Oh, {Ki Wan} and Kim, {Dae Joong} and Yun, {Young Won} and Hwang, {Se Jin} and Lee, {Sung Eun} and Hong, {Jin Tae}",

year = "2004",

month = jul,

day = "15",

doi = "10.1016/j.yexcr.2004.03.034",

language = "English",

volume = "297",

pages = "424--433",

journal = "Experimental Cell Research",

issn = "0014-4827",

publisher = "Elsevier Inc.",

number = "2",

}

Park, KS, Lee, RD, Kang, SK, Han, SY, Park, KL, Yang, KH, Song, YS, Park, HJ, Lee, YM, Yun, YP, Oh, KW, Kim, DJ, Yun, YW, Hwang, SJ, Lee, SE & Hong, JT 2004, 'Neuronal differentiation of embryonic midbrain cells by upregulation of peroxisome proliferator-activated receptor-gamma via the JNK-dependent pathway', Experimental Cell Research, vol. 297, no. 2, pp. 424-433. https://doi.org/10.1016/j.yexcr.2004.03.034

TY - JOUR

T1 - Neuronal differentiation of embryonic midbrain cells by upregulation of peroxisome proliferator-activated receptor-gamma via the JNK-dependent pathway

AU - Park, Ki Sook

AU - Lee, Rhee Da

AU - Kang, Sun Kyung

AU - Han, Soon Young

AU - Park, Kui Lae

AU - Yang, Ki Hwa

AU - Song, Youn Sook

AU - Park, Hye Ji

AU - Lee, Yoot Mo

AU - Yun, Yeo Pyo

AU - Oh, Ki Wan

AU - Kim, Dae Joong

AU - Yun, Young Won

AU - Hwang, Se Jin

AU - Lee, Sung Eun

AU - Hong, Jin Tae

PY - 2004/7/15

Y1 - 2004/7/15

N2 - Our previous study showed that the peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonist 15-deoxy-PGJ2 has the promoting ability to differentiate neuronal PC12 cells. To expand our study, the effect of 15-deoxy-PGJ2 on the differentiation of embryonic midbrain cells into dopaminergic neuronal cells was investigated in this study. The relationship between cell differentiation with activation of PPAR-γ and the possible signal pathway were also investigated. 15-Deoxy-PGJ2 increased neurite extension, a typical characteristic of the differentiation of embryonic midbrain cells isolated from 12-day rat embryos in a dose-dependent manner. The expression of differentiation markers, neurofilament, tyrosine hydroxylase, and nestin, was also increased by the treatment of 15-deoxy-PGJ2. Consistent with the increasing effect on cell differentiation, 15-deoxy-PGJ2 increased the expression and transcriptional activity of PPAR-γ in cultured embryonic midbrain cells. In addition, the expression of PPAR-γ and NeuN in the differentiated neuron of fetus (17 days) and adult rat brain was co-localized. Furthermore, treatment of PPAR-γ antagonist bisphenol A diglycidyl ether blocked 15-deoxy-PGJ2-induced neuronal differentiation of embryonic midbrain cells and expression of PPAR-γ. To elucidate the possible signal pathway, the activation of mitogenic-activated protein (MAP) kinase family was determined. 15-Deoxy-PGJ2 (0.5 μM) increased activation of Jun N-terminal kinase (JNK) and p38 kinase but not extra-signal response kinase (ERK). In addition, NGF (50 ng/ml) further increased the 15-deoxy-PGJ 2-induced JNK activation. Moreover, pretreatment of specific inhibitor of JNK SP600125 blocked the 15-deoxy-PGJ2-induced JNK activation. This inhibition correlated well with the inhibition of neurite extension and expression of PPAR-γ induced by 15-deoxy-PGJ2. The present results therefore indicate that 15-deoxy-PGJ2 stimulates differentiation of embryonic midbrain cells into dopaminergic neuronal cells, and its effect may be PPAR-γ and JNK signal pathway dependent.

AB - Our previous study showed that the peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonist 15-deoxy-PGJ2 has the promoting ability to differentiate neuronal PC12 cells. To expand our study, the effect of 15-deoxy-PGJ2 on the differentiation of embryonic midbrain cells into dopaminergic neuronal cells was investigated in this study. The relationship between cell differentiation with activation of PPAR-γ and the possible signal pathway were also investigated. 15-Deoxy-PGJ2 increased neurite extension, a typical characteristic of the differentiation of embryonic midbrain cells isolated from 12-day rat embryos in a dose-dependent manner. The expression of differentiation markers, neurofilament, tyrosine hydroxylase, and nestin, was also increased by the treatment of 15-deoxy-PGJ2. Consistent with the increasing effect on cell differentiation, 15-deoxy-PGJ2 increased the expression and transcriptional activity of PPAR-γ in cultured embryonic midbrain cells. In addition, the expression of PPAR-γ and NeuN in the differentiated neuron of fetus (17 days) and adult rat brain was co-localized. Furthermore, treatment of PPAR-γ antagonist bisphenol A diglycidyl ether blocked 15-deoxy-PGJ2-induced neuronal differentiation of embryonic midbrain cells and expression of PPAR-γ. To elucidate the possible signal pathway, the activation of mitogenic-activated protein (MAP) kinase family was determined. 15-Deoxy-PGJ2 (0.5 μM) increased activation of Jun N-terminal kinase (JNK) and p38 kinase but not extra-signal response kinase (ERK). In addition, NGF (50 ng/ml) further increased the 15-deoxy-PGJ 2-induced JNK activation. Moreover, pretreatment of specific inhibitor of JNK SP600125 blocked the 15-deoxy-PGJ2-induced JNK activation. This inhibition correlated well with the inhibition of neurite extension and expression of PPAR-γ induced by 15-deoxy-PGJ2. The present results therefore indicate that 15-deoxy-PGJ2 stimulates differentiation of embryonic midbrain cells into dopaminergic neuronal cells, and its effect may be PPAR-γ and JNK signal pathway dependent.

KW - 15-Deoxy-PGJ

KW - Differentiation

KW - Embryonic midbrain cell

KW - JNK

KW - PPAR-γ

UR - http://www.scopus.com/inward/record.url?scp=2942726088&partnerID=8YFLogxK

U2 - 10.1016/j.yexcr.2004.03.034

DO - 10.1016/j.yexcr.2004.03.034

M3 - Article

C2 - 15212945

AN - SCOPUS:2942726088

SN - 0014-4827

VL - 297

SP - 424

EP - 433

JO - Experimental Cell Research

JF - Experimental Cell Research

IS - 2

ER -

Neuronal differentiation of embryonic midbrain cells by upregulation of peroxisome proliferator-activated receptor-gamma via the JNK-dependent pathway

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