title: Am80 induces neuronal differentiation via increased tropomyosin-related kinase B expression in a human neuroblastoma SH-SY5Y cell line.
abstract: Am80, a synthetic retinoid, has been used in differentiation therapy for acute promyelocytic leukemia (APL). All-trans retinoic acid (ATRA) as one of natural retinoid has been also used to treat APL. ATRA treatment causes neuronal differentiation by inducing tropomyosin-related kinase B (TrkB) expression and increasing the sensitivity to brain-derived neurotrophic factor (BDNF), a TrkB ligand. In the present study, we investigated the effects of Am80 on neuronal differentiation, BDNF sensitivity and TrkB expression in human neuroblastoma SH-SY5Y cells. Treatment with Am80 induced morphological differentiation of neurite outgrowth and increased the expression of GAP43 mRNA, a neuronal differentiation marker. Additionally, TrkB protein was also increased, and exogenous BDNF stimulation after treatment with Am80 induced greater neurite outgrowth than without BDNF treatment. These results suggest that Am80 induced neuronal differentiation by increasing TrkB expression and BDNF sensitivity.
authors.affiliation: Department of Immunological and Molecular Pharmacology, Faculty of Pharmaceutical Science, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Shiohira
authors.forename: Akira
authors.initials: A
authors.lastname: Kitaoka
authors.forename: Munechika
authors.initials: M
authors.lastname: Enjoji
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Uno
authors.forename: Manabu
authors.initials: M
authors.lastname: Nakashima
mesh_terms: D001565:Benzoates / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D019922:GAP-43 Protein / Q000096:biosynthesis; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D016501:Neurites / Q000201:enzymology; D009447:Neuroblastoma / Q000201:enzymology* / Q000473:pathology; D020813:Receptor, trkB / Q000096:biosynthesis*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
chemical_list: D001565:Benzoates; D019208:Brain-Derived Neurotrophic Factor; D019922:GAP-43 Protein; D009363:Neoplasm Proteins; D013764:Tetrahydronaphthalenes; C061133:tamibarotene; D020813:Receptor, trkB