title: Rosiglitazone promotes neurite outgrowth and mitochondrial function in N2A cells via PPARgamma pathway.
abstract: Several pieces of evidence indicate that peroxisome proliferator-activated receptor gamma (PPARγ) stimulation promotes neuronal differentiation. However, to date, the effects of a synthetic PPARγ agonist (Rosiglitazone, Rosi) on neurite outgrowth have not yet been well described. Here we have evaluated the effects of Rosi on neurite outgrowth and mitochondrial function in the mouse neuroblastoma Neuro 2a (N2A) cell line. Our results show that Rosi promotes neurite outgrowth of N2A cells and significantly increases the population of neurite-bearing cells, with apparent increase of intracellular calcium and the expression of calmodulin-dependent kinase I (CaMKI). Rosi also increases the intracellular cAMP and expression of both protein kinase A (PKA) and cAMP response element binding protein (CREB). Phosphorylation of CREB was also detected in the Rosi treated N2A cells. Moreover, Rosi significantly increases the transcription of AMP-activated kinase (AMPK) and Sirtuin 1 (SIRT1). Besides, the expression of PPAR coactivator 1α (PGC1α), as well as the mRNA level its downstream genes, including nuclear respiratory factors 1 and 2 (NRF1 and NRF2) and mitochondrial transcription factor A (Tfam) were induced by Rosi treatments. Furthermore, Rosi increases the level of ATP, D-loop, and mitochondrial mass in N2A cells. Collectively, these findings provide an array of evidence that PPARγ activation provides beneficial neuronal networks within neurite outgrowth.
authors.affiliation: Department of Life Science, Fu Jen Catholic University, New Taipei City 242, Taiwan. Electronic address: cmcphd@gmail.com.
authors.forename: Ming-Chang
authors.initials: MC
authors.lastname: Chiang
authors.affiliation: Department of Biochemistry and Molecular Biology, Chang Gung University, Tao Yuan 333, Taiwan.
authors.forename: Yi-Chuan
authors.initials: YC
authors.lastname: Cheng
authors.affiliation: Department of Life Science, Fu Jen Catholic University, New Taipei City 242, Taiwan; Graduate Institute of Applied Science and Engineering, Fu Jen Catholic University, New Taipei City 242, Taiwan.
authors.forename: Han-Min
authors.initials: HM
authors.lastname: Chen
authors.affiliation: Department of Life Science, Fu Jen Catholic University, New Taipei City 242, Taiwan.
authors.forename: Yao-Jen
authors.initials: YJ
authors.lastname: Liang
authors.affiliation: Department of International Business, Ming Chuan University, Taipei 111, Taiwan.
authors.forename: Chia-Hui
authors.initials: CH
authors.lastname: Yen
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D051379:Mice; D016501:Neurites / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D047495:PPAR gamma / Q000378:metabolism*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000378:metabolism*
chemical_list: D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone
keywords: Mitochondrial function; Neurite outgrowth; PGC1α; PPARγ; Rosiglitazone