Peroxisome proliferator-activated receptor γ is a novel target of the nerve growth factor signaling pathway in PC12 cells

被引:37
作者
Fuenzalida, KM
Aguilera, MC
Piderit, DG
Ramos, PC
Contador, D
Quiñones, V
Rigotti, A
Bronfman, FC
Bronfman, M
机构
[1] Pontificia Univ Catolica Chile, Fac Ciencias Biol, Ctr Regulac Celular & Patol, Dept Cellular & Mol Biol, Santiago, Chile
[2] Pontificia Univ Catolica Chile, Fac Biol Sci, Millenium Inst Fundamental & Appl Biol, Santiago, Chile
[3] Pontificia Univ Catolica Chile, Fac Med, Dept Gastroenterol, Santiago, Chile
关键词
D O I
10.1074/jbc.M409447200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Peroxisome proliferator- activated receptor gamma ( PPARgamma), a member of the nuclear receptor superfamily, is subject to considerable interest because of its role in adipocyte differentiation, metabolic control, and anti- inflammatory action. PPARgamma research in brain cells is presently focused on glial PPARgamma because of its potential as a pharmacological target in the treatment of neurodegenerative diseases with an inflammatory component. In neurons PPARgamma function is far from clear, and PPARgamma agonist-dependent and -independent effects on cell survival or differentiation have been reported. We used PC12 cells, widely used to study neuronal signaling, such as nerve growth factor (NGF)-induced differentiation and survival or epidermal growth factor-dependent cell proliferation to dissect the possible involvement of PPARgamma in these pathways. We show that NGF but not epidermal growth factor increases the transcriptional activity of PPARgamma, and modulates the expression of this transcription factor. Because NGF signals through the tyrosine kinase (TrkA) NGF receptor and/ or the p75(NTR) receptor, we used rescue experiments with a PC12 cell mutant lacking TrkA to show that NGF- induced PPARgamma activation is dependent on TrkA activation. Our results point out PPARgamma as a novel target of the TrkA-mediated neuronal cell survival and differentiating pathway and suggest a potential new inflammatory-independent therapeutic approach for pharmacological intervention in neurological disorders.
引用
收藏
页码:9604 / 9609
页数:6
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