Human adipose tissue-derived multilineage progenitor cells exposed to oxidative stress induce neurite outgrowth in PC12 cells through p38 MAPK signaling

Mariko Moriyama, Hiroyuki Moriyama, Ayaka Ueda, Yusuke Nishibata, Hanayuki Okura, Akihiro Ichinose, Akifumi Matsuyama, Takao Hayakawa

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Background: Adipose tissues contain populations of pluripotent mesenchymal stem cells that also secrete various cytokines and growth factors to support repair of damaged tissues. In this study, we examined the role of oxidative stress on human adipose-derived multilineage progenitor cells (hADMPCs) in neurite outgrowth in cells of the rat pheochromocytoma cell line (PC12).Results: We found that glutathione depletion in hADMPCs, caused by treatment with buthionine sulfoximine (BSO), resulted in the promotion of neurite outgrowth in PC12 cells through upregulation of bone morphogenetic protein 2 (BMP2) and fibroblast growth factor 2 (FGF2) transcription in, and secretion from, hADMPCs. Addition of N-acetylcysteine, a precursor of the intracellular antioxidant glutathione, suppressed the BSO-mediated upregulation of BMP2 and FGF2. Moreover, BSO treatment caused phosphorylation of p38 MAPK in hADMPCs. Inhibition of p38 MAPK was sufficient to suppress BMP2 and FGF2 expression, while this expression was significantly upregulated by overexpression of a constitutively active form of MKK6, which is an upstream molecule from p38 MAPK.Conclusions: Our results clearly suggest that glutathione depletion, followed by accumulation of reactive oxygen species, stimulates the activation of p38 MAPK and subsequent expression of BMP2 and FGF2 in hADMPCs. Thus, transplantation of hADMPCs into neurodegenerative lesions such as stroke and Parkinson's disease, in which the transplanted hADMPCs are exposed to oxidative stress, can be the basis for simple and safe therapies.

Original languageEnglish
Article number21
JournalBMC Cell Biology
Volume13
DOIs
Publication statusPublished - 07-08-2012

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PC12 Cells
p38 Mitogen-Activated Protein Kinases
Adipose Tissue
Oxidative Stress
Stem Cells
Bone Morphogenetic Protein 2
Fibroblast Growth Factor 2
Buthionine Sulfoximine
Glutathione
Up-Regulation
Pluripotent Stem Cells
Acetylcysteine
Neuronal Outgrowth
Mesenchymal Stromal Cells
Parkinson Disease
Reactive Oxygen Species
Intercellular Signaling Peptides and Proteins
Antioxidants
Transplantation
Stroke

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

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title = "Human adipose tissue-derived multilineage progenitor cells exposed to oxidative stress induce neurite outgrowth in PC12 cells through p38 MAPK signaling",
abstract = "Background: Adipose tissues contain populations of pluripotent mesenchymal stem cells that also secrete various cytokines and growth factors to support repair of damaged tissues. In this study, we examined the role of oxidative stress on human adipose-derived multilineage progenitor cells (hADMPCs) in neurite outgrowth in cells of the rat pheochromocytoma cell line (PC12).Results: We found that glutathione depletion in hADMPCs, caused by treatment with buthionine sulfoximine (BSO), resulted in the promotion of neurite outgrowth in PC12 cells through upregulation of bone morphogenetic protein 2 (BMP2) and fibroblast growth factor 2 (FGF2) transcription in, and secretion from, hADMPCs. Addition of N-acetylcysteine, a precursor of the intracellular antioxidant glutathione, suppressed the BSO-mediated upregulation of BMP2 and FGF2. Moreover, BSO treatment caused phosphorylation of p38 MAPK in hADMPCs. Inhibition of p38 MAPK was sufficient to suppress BMP2 and FGF2 expression, while this expression was significantly upregulated by overexpression of a constitutively active form of MKK6, which is an upstream molecule from p38 MAPK.Conclusions: Our results clearly suggest that glutathione depletion, followed by accumulation of reactive oxygen species, stimulates the activation of p38 MAPK and subsequent expression of BMP2 and FGF2 in hADMPCs. Thus, transplantation of hADMPCs into neurodegenerative lesions such as stroke and Parkinson's disease, in which the transplanted hADMPCs are exposed to oxidative stress, can be the basis for simple and safe therapies.",
author = "Mariko Moriyama and Hiroyuki Moriyama and Ayaka Ueda and Yusuke Nishibata and Hanayuki Okura and Akihiro Ichinose and Akifumi Matsuyama and Takao Hayakawa",
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Human adipose tissue-derived multilineage progenitor cells exposed to oxidative stress induce neurite outgrowth in PC12 cells through p38 MAPK signaling. / Moriyama, Mariko; Moriyama, Hiroyuki; Ueda, Ayaka; Nishibata, Yusuke; Okura, Hanayuki; Ichinose, Akihiro; Matsuyama, Akifumi; Hayakawa, Takao.

In: BMC Cell Biology, Vol. 13, 21, 07.08.2012.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Human adipose tissue-derived multilineage progenitor cells exposed to oxidative stress induce neurite outgrowth in PC12 cells through p38 MAPK signaling

AU - Moriyama, Mariko

AU - Moriyama, Hiroyuki

AU - Ueda, Ayaka

AU - Nishibata, Yusuke

AU - Okura, Hanayuki

AU - Ichinose, Akihiro

AU - Matsuyama, Akifumi

AU - Hayakawa, Takao

PY - 2012/8/7

Y1 - 2012/8/7

N2 - Background: Adipose tissues contain populations of pluripotent mesenchymal stem cells that also secrete various cytokines and growth factors to support repair of damaged tissues. In this study, we examined the role of oxidative stress on human adipose-derived multilineage progenitor cells (hADMPCs) in neurite outgrowth in cells of the rat pheochromocytoma cell line (PC12).Results: We found that glutathione depletion in hADMPCs, caused by treatment with buthionine sulfoximine (BSO), resulted in the promotion of neurite outgrowth in PC12 cells through upregulation of bone morphogenetic protein 2 (BMP2) and fibroblast growth factor 2 (FGF2) transcription in, and secretion from, hADMPCs. Addition of N-acetylcysteine, a precursor of the intracellular antioxidant glutathione, suppressed the BSO-mediated upregulation of BMP2 and FGF2. Moreover, BSO treatment caused phosphorylation of p38 MAPK in hADMPCs. Inhibition of p38 MAPK was sufficient to suppress BMP2 and FGF2 expression, while this expression was significantly upregulated by overexpression of a constitutively active form of MKK6, which is an upstream molecule from p38 MAPK.Conclusions: Our results clearly suggest that glutathione depletion, followed by accumulation of reactive oxygen species, stimulates the activation of p38 MAPK and subsequent expression of BMP2 and FGF2 in hADMPCs. Thus, transplantation of hADMPCs into neurodegenerative lesions such as stroke and Parkinson's disease, in which the transplanted hADMPCs are exposed to oxidative stress, can be the basis for simple and safe therapies.

AB - Background: Adipose tissues contain populations of pluripotent mesenchymal stem cells that also secrete various cytokines and growth factors to support repair of damaged tissues. In this study, we examined the role of oxidative stress on human adipose-derived multilineage progenitor cells (hADMPCs) in neurite outgrowth in cells of the rat pheochromocytoma cell line (PC12).Results: We found that glutathione depletion in hADMPCs, caused by treatment with buthionine sulfoximine (BSO), resulted in the promotion of neurite outgrowth in PC12 cells through upregulation of bone morphogenetic protein 2 (BMP2) and fibroblast growth factor 2 (FGF2) transcription in, and secretion from, hADMPCs. Addition of N-acetylcysteine, a precursor of the intracellular antioxidant glutathione, suppressed the BSO-mediated upregulation of BMP2 and FGF2. Moreover, BSO treatment caused phosphorylation of p38 MAPK in hADMPCs. Inhibition of p38 MAPK was sufficient to suppress BMP2 and FGF2 expression, while this expression was significantly upregulated by overexpression of a constitutively active form of MKK6, which is an upstream molecule from p38 MAPK.Conclusions: Our results clearly suggest that glutathione depletion, followed by accumulation of reactive oxygen species, stimulates the activation of p38 MAPK and subsequent expression of BMP2 and FGF2 in hADMPCs. Thus, transplantation of hADMPCs into neurodegenerative lesions such as stroke and Parkinson's disease, in which the transplanted hADMPCs are exposed to oxidative stress, can be the basis for simple and safe therapies.

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