Activation of NPFF2receptor stimulates neurite outgrowth in Neuro 2A cells through activation of ERK signaling pathway.
Neurite outgrowth is an important process in neural regeneration and plasticity, especially after neural injury, and recent evidence indicates that several Gαi/oprotein-coupled receptors play an important role in neurite outgrowth. The neuropeptide (NP)FF system contains two Gαi/oprotein-coupled receptors, NPFF1and NPFF2receptors, which are mainly distributed in the central nervous system. The aim of the present study was to determine whether the NPFF system is involved in neurite outgrowth in Neuro 2A cells. We showed that Neuro 2A cells endogenously expressed NPFF2receptor, and the NPFF2receptor agonist dNPA inhibited cyclic adenosine monophosphate (cAMP) production stimulated by forskolin in Neuro 2A cells. We also demonstrated that NPFF and dNPA dose-dependently induced neurite outgrowth in Neuro 2A cells, which was completely abolished by the NPFF receptor antagonist RF9. Pretreatment with mitogen-activated protein kinase inhibitors PD98059 and U0126 decreased dNPA-induced neurite outgrowth. In addition, dNPA increased phosphorylation of extracellular signal-regulated kinase (ERK) in Neuro 2A cells, which was completely antagonized by pretreatment with U0126. Our results suggest that activation of NPFF2receptor stimulates neurite outgrowth in Neuro 2A cells through activation of the ERK signaling pathway. Moreover, NPFF2receptor may be a potential therapeutic target for neural injury and degeneration in the future.
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou, 730000, PR China.
Hong-Ping
HP
Yu
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou, 730000, PR China.
Nan
N
Zhang
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou, 730000, PR China.
Ting
T
Zhang
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou, 730000, PR China.
Zi-Long
ZL
Wang
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou, 730000, PR China.
Ning
N
Li
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou, 730000, PR China.
Hong-Hai
HH
Tang
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou, 730000, PR China.
Run
R
Zhang
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou, 730000, PR China.
Meng-Na
MN
Zhang
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou, 730000, PR China.
Biao
B
Xu
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou, 730000, PR China. Electronic address: fangq@lzu.edu.cn.
Quan
Q
Fang
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, 199 Donggang West Road, Lanzhou, 730000, PR China. Electronic address: wangrui@lzu.edu.cn.
Rui
R
Wang
D000818:Animals; D049108:Cell Enlargement; D002460:Cell Line; D005576:Colforsin / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression; D020935:MAP Kinase Signaling System; D051379:Mice; D016501:Neurites / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D018013:Receptors, Neuropeptide / Q000819:agonists / Q000235:genetics / Q000378:metabolism*
D009842:Oligopeptides; D018013:Receptors, Neuropeptide; C000611306:dNPA peptide; C083929:neuropeptide FF receptor; D005576:Colforsin; D000242:Cyclic AMP; D048049:Extracellular Signal-Regulated MAP Kinases
MEK/ERK signaling pathway; NPFF(2) receptor; Neurite outgrowth; Neuro 2A cells