RRC ID 19647
Author Hamada N, Fujita Y, Tanaka A, Naoi M, Nozawa Y, Ono Y, Kitagawa Y, Tomimori N, Kiso Y, Ito M.
Title Metabolites of sesamin, a major lignan in sesame seeds, induce neuronal differentiation in PC12 cells through activation of ERK1/2 signaling pathway.
Journal J Neural Transm (Vienna)
Abstract Sesamin, a major lignan in sesame seeds, exhibits various health benefits. Here, we investigated effects of sesamin, its stereoisomer episesamin, and their metabolites on neuronal differentiation in rat pheochromocytoma PC12 cells. Among all compounds tested, primary metabolites of sesamin and episesamin, SC-1 and EC-1 {S- and R-epimer of 2-(3,4-methylenedioxyphenyl)-6-(3,4-dihydroxyphenyl)-3,7-dioxabicyclo [3.3.0]octane}, were the most potent to induce neuronal differentiation. SC-1 alone induced neuronal differentiation through extracellular signal-regulated kinase (ERK) 1/2 activation that is essential for nerve growth factor (NGF)-induced neuronal differentiation, as shown by the suppression with MEK1/2 inhibitors, PD98059 and U0126. However, SC-1 did not increase phosphorylation of TrkA, a high-affinity NGF receptor, and a TrkA inhibitor, K252a, did not affect SC-1-induced neuronal differentiation. Furthermore, SC-1 potentiated neuronal differentiation in cells co-treated with NGF, which was associated with enhanced ERK1/2 activation and increased expression of neuronal differentiation markers. Interestingly, when treated with SC-1 and a high dose of NGF, formation of synaptic connections and synaptophysin accumulation at the neurite terminals were markedly enhanced. These results indicate that (1) SC-1 alone induces neuronal differentiation, (2) SC-1 potentiates neuronal differentiation in NGF-treated cells, (3) SC-1 enhances formation of synaptic connections in cells treated with a high dose of NGF, all of which are associated with ERK1/2 activation. It is therefore concluded that SC-1 may promote neuronal differentiation by tapping into the ERK1/2-MAPK (mitogen-activated protein kinase) signaling pathway downstream from the TrkA receptor in PC12 cells.
Volume 116(7)
Pages 841-52
Published 2009-7
DOI 10.1007/s00702-009-0250-9
PMID 19533291
MeSH Animals Antioxidants / pharmacology Cell Differentiation / drug effects Cell Differentiation / physiology Dioxoles / chemistry Dioxoles / metabolism Dioxoles / pharmacology* Dose-Response Relationship, Drug Drug Synergism Lignans / chemistry Lignans / metabolism Lignans / pharmacology* MAP Kinase Signaling System / drug effects* MAP Kinase Signaling System / physiology Mitogen-Activated Protein Kinase 3 / drug effects* Mitogen-Activated Protein Kinase 3 / metabolism Nerve Growth Factor / drug effects Nerve Growth Factor / metabolism Nerve Growth Factor / pharmacology Neural Pathways / drug effects Neural Pathways / growth & development Neural Pathways / metabolism Neurogenesis / drug effects Neurogenesis / physiology Neurons / drug effects* Neurons / metabolism PC12 Cells Phosphorylation / drug effects Rats Receptor, trkA / agonists Receptor, trkA / antagonists & inhibitors Receptor, trkA / metabolism Synapses / drug effects Synapses / metabolism Synaptophysin / drug effects Synaptophysin / metabolism
IF 2.779
Times Cited 19
Human and Animal Cells PC-12 (RCB0009)