title: Visfatin induces neurite outgrowth in PC12 cells via ERK1/2 signaling pathway.
abstract: The angiogenic and inflammatory functions of visfatin and its effect on vascular cells, are fairly well known. However, its role within the nervous system remains largely unclear. To gain insight into this area, we studied the neuritogenic effect of visfatin on PC12 rat pheochromocytoma cells. We investigated whether visfatin gene expression, which is upregulated by hypoxia in cancer cells, is associated with neuritogenesis in PC12 cells. Using RT-PCR, Western blot analysis, ELISA, morphological observations, and immunostaining, we initially showed that CoCl(2), a hypoxic mimetic agent, upregulated visfatin gene expression along with neurite outgrowth in PC12 cells. We also showed that visfatin stimulated neurite outgrowth in PC12 cells. Moreover, in PC12 cells, visfatin evoked the activation of the extracellular signal-regulated kinase 1/2 (ERK1/2), which is closely linked to neuritogenesis. Visfatin-induced outgrowth of neurites was prevented by inhibition of the ERK1/2 pathway. Taken together, our results demonstrate for the first time that visfatin induces neurite outgrowth in PC12 cells via the activation of an ERK-dependent pathway, and suggest that visfatin may exert various biological, physiological, and pathological functions in not only the vascular system but also the nervous system.
authors.affiliation: Department of Dental Pharmacology, Yangsan Campus of Pusan National University, Yangsan 626-870, South Korea.
authors.forename: Young-Soon
authors.initials: YS
authors.lastname: Kang
authors.affiliation: Department of Oral Physiology, School of Dentistry, Yangsan Campus of Pusan National University, Yangsan 626-870, South Korea; Research Institute for Oral Biotechnology, Yangsan Campus of Pusan National University, Yangsan 626-870, South Korea.
authors.forename: Moon-Kyoung
authors.initials: MK
authors.lastname: Bae
authors.affiliation: Department of Physiology, School of Medicine, Yangsan Campus of Pusan National University, Yangsan 626-870, South Korea.
authors.forename: Jee-Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Anatomy and Neurobiology, School of Medicine, Kyunghee University, Seoul 130-701, South Korea.
authors.forename: Joo-Won
authors.initials: JW
authors.lastname: Jeong
authors.affiliation: Department of Dental Pharmacology, Yangsan Campus of Pusan National University, Yangsan 626-870, South Korea; Research Institute for Oral Biotechnology, Yangsan Campus of Pusan National University, Yangsan 626-870, South Korea.
authors.forename: Il
authors.initials: I
authors.lastname: Yun
authors.affiliation: Department of Dental Pharmacology, Yangsan Campus of Pusan National University, Yangsan 626-870, South Korea; Research Institute for Oral Biotechnology, Yangsan Campus of Pusan National University, Yangsan 626-870, South Korea.
authors.forename: Hye-Ock
authors.initials: HO
authors.lastname: Jang
authors.affiliation: Department of Dental Pharmacology, Yangsan Campus of Pusan National University, Yangsan 626-870, South Korea; Research Institute for Oral Biotechnology, Yangsan Campus of Pusan National University, Yangsan 626-870, South Korea; Medical Research Institute, Yangsan Campus of Pusan National University, Yangsan 626-870, South Korea. Electronic address: skbae@pusan.ac.kr.
authors.forename: Soo-Kyung
authors.initials: SK
authors.lastname: Bae
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D003035:Cobalt / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000187:drug effects / Q000502:physiology*; D016501:Neurites / Q000187:drug effects*; D054409:Nicotinamide Phosphoribosyltransferase / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D012844:Sincalide / Q000378:metabolism
chemical_list: D007211:Indoles; D015842:Serine Proteinase Inhibitors; D003035:Cobalt; C007293:DAPI; D054409:Nicotinamide Phosphoribosyltransferase; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C018021:cobaltous chloride; D012844:Sincalide