title: Nerve growth factor enhances the CRE-dependent transcriptional activity activated by nobiletin in PC12 cells.
abstract: Prevention and treatment of Alzheimer disease are urgent problems for elderly people in developed countries. We previously reported that nobiletin, a poly-methoxylated flavone from the citrus peel, improved the symptoms in various types of animal models of memory loss and activated the cAMP responsive element (CRE)-dependent transcription in PC12 cells. Nobiletin activated the cAMP/PKA/MEK/Erk/MAPK signaling pathway without using the TrkA signaling activated by nerve growth factor (NGF). Here, we examined the effect of combination of nobiletin and NGF on the CRE-dependent transcription in PC12 cells. Although NGF alone had little effect on the CRE-dependent transcription, NGF markedly enhanced the CRE-dependent transcription induced by nobiletin. The NGF-induced enhancement was neutralized by a TrkA antagonist, K252a. This effect of NGF was effective on the early signaling event elicited by nobiletin. These results suggested that there was crosstalk between NGF and nobiletin signaling in activating the CRE-dependent transcription in PC12 cells.
authors.affiliation: a Department of Oral Anatomy and Developmental Biology, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555, Japan.
authors.forename: Jiro
authors.initials: J
authors.lastname: Takito
authors.affiliation: b Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Kimura
authors.affiliation: c Sankyo Holdings Co., Ltd., 573-13 Denbou, Fuji-shi, Shizuoka, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Kajima
authors.affiliation: d Department of Biomolecular Engineering, Graduate School of Engineering, Tohoku University, 6-6-07 Aobayama, Sendai, Miyagi, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Uozumi
authors.affiliation: e Kansei Fukushi Research Center, Tohoku Fukushi University, 6-149-1 Kunimigaoka, Aoba-ku, Sendai, Miyagi, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: f Laboratory of Medicinal Plant Science, School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Yokosuka
authors.affiliation: f Laboratory of Medicinal Plant Science, School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Mimaki
authors.affiliation: a Department of Oral Anatomy and Developmental Biology, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: b Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, Japan.|e Kansei Fukushi Research Center, Tohoku Fukushi University, 6-149-1 Kunimigaoka, Aoba-ku, Sendai, Miyagi, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ohizumi
mesh_terms: D000818:Animals; D051786:Cyclic AMP Response Element Modulator / Q000235:genetics / Q000378:metabolism*; D004357:Drug Synergism; D047309:Flavones / Q000302:isolation & purification / Q000494:pharmacology*; D020932:Nerve Growth Factor / Q000494:pharmacology*; D016716:PC12 Cells; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology*
chemical_list: D047309:Flavones; D010936:Plant Extracts; D051786:Cyclic AMP Response Element Modulator; D020932:Nerve Growth Factor; C008661:nobiletin
keywords: Alzheimer disease; CRE-dependent transcription; PC12 cells; cellules PC12; facteur de croissance neuronal; flavone; maladie d’Alzheimer; nerve growth factor; neuron; neurone; nobiletin; nobilétine; transcription dépendante des CRE