title: Neuropeptide FF activates ERK and NF kappa B signal pathways in differentiated SH-SY5Y cells.
abstract: Neuropeptide FF (NPFF) has been reported to play important roles in regulating diverse biological processes. However, little attention has been focused on the downstream signal transduction pathway of NPFF. Here, we used the differentiated neuroblastoma cell line, dSH-SY5Y, which endogenously expresses hNPFF2 receptor, to investigate the signal transduction downstream of NPFF. In particular we investigated the regulation of the extracellular signal-regulated protein kinase (ERK) and the nuclear factor kappa B (NF-κB) pathways by NPFF in these cells. NPFF rapidly and transiently stimulated ERK. H89, a selective inhibitor of cyclic AMP-dependent protein kinase A (PKA), inhibited the NPFF-activated ERK pathway, indicating the involvement of PKA in the NPFF-induced ERK activation. Down-regulation of nitric oxide synthases also attenuated NPFF-induced ERK activation, suggesting that a nitric oxide synthase-dependent pathway is involved. Moreover, the core upstream components of the NF-κB pathway were also significantly activated in response to NPFF, suggesting that the NF-κB pathway is involved in the signal transduction pathway of NPFF. Collectively, these data demonstrate that nitric oxide synthases are involved in the signal transduction pathway of NPFF, and provide the first evidence for the interaction between NPFF and the NF-κB pathway. These advances in our interpretation of the NPFF pathway mechanism will aid the comprehensive understanding of its function and provide novel molecular insight for further study of the NPFF system.
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Life Sciences, Lanzhou University, Lanzhou, Gansu 730000, PR China.
authors.forename: Yu-long
authors.initials: YL
authors.lastname: Sun
authors.forename: Xiao-yuan
authors.initials: XY
authors.lastname: Zhang
authors.forename: Ning
authors.initials: N
authors.lastname: He
authors.forename: Tao
authors.initials: T
authors.lastname: Sun
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhuang
authors.forename: Quan
authors.initials: Q
authors.lastname: Fang
authors.forename: Kai-rong
authors.initials: KR
authors.lastname: Wang
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D018013:Receptors, Neuropeptide / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D007546:Isoquinolines; D016328:NF-kappa B; D009842:Oligopeptides; D047428:Protein Kinase Inhibitors; D018013:Receptors, Neuropeptide; D013449:Sulfonamides; C083929:neuropeptide FF receptor; D009569:Nitric Oxide; C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide; D048049:Extracellular Signal-Regulated MAP Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide