RRC ID 34820
著者 Moriyama M, Moriyama H, Ueda A, Nishibata Y, Okura H, Ichinose A, Matsuyama A, Hayakawa T.
タイトル Human adipose tissue-derived multilineage progenitor cells exposed to oxidative stress induce neurite outgrowth in PC12 cells through p38 MAPK signaling.
ジャーナル BMC Cell Biol
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.
巻・号 13
ページ 21
公開日 2012-8-7
DOI 10.1186/1471-2121-13-21
PII 1471-2121-13-21
PMID 22870983
PMC PMC3465210
MeSH Acetylcysteine / pharmacology Animals Bone Morphogenetic Protein 2 / genetics Bone Morphogenetic Protein 2 / metabolism Buthionine Sulfoximine / pharmacology* Cell Differentiation / drug effects Cell Line Fibroblast Growth Factor 2 / genetics Fibroblast Growth Factor 2 / metabolism Glutathione / metabolism Humans MAP Kinase Kinase 6 / metabolism Neurites / drug effects Neurites / metabolism Oxidative Stress / drug effects* PC12 Cells Phosphorylation Rats Reactive Oxygen Species / metabolism Signal Transduction Smad Proteins / metabolism Stem Cells / cytology Stem Cells / drug effects Stem Cells / metabolism* Up-Regulation / drug effects p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors p38 Mitogen-Activated Protein Kinases / metabolism*
IF 3.066
引用数 22
WOS 分野 CELL BIOLOGY
リソース情報
遺伝子材料 pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393) CSII-EF-RfA (RDB04387).