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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2009-6-24
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1435-1463
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
116
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
841-52
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:19533291-Animals, pubmed-meshheading:19533291-Antioxidants, pubmed-meshheading:19533291-Cell Differentiation, pubmed-meshheading:19533291-Dioxoles, pubmed-meshheading:19533291-Dose-Response Relationship, Drug, pubmed-meshheading:19533291-Drug Synergism, pubmed-meshheading:19533291-Lignans, pubmed-meshheading:19533291-MAP Kinase Signaling System, pubmed-meshheading:19533291-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:19533291-Nerve Growth Factor, pubmed-meshheading:19533291-Neural Pathways, pubmed-meshheading:19533291-Neurogenesis, pubmed-meshheading:19533291-Neurons, pubmed-meshheading:19533291-PC12 Cells, pubmed-meshheading:19533291-Phosphorylation, pubmed-meshheading:19533291-Rats, pubmed-meshheading:19533291-Receptor, trkA, pubmed-meshheading:19533291-Synapses, pubmed-meshheading:19533291-Synaptophysin
pubmed:year
2009
pubmed:articleTitle
Metabolites of sesamin, a major lignan in sesame seeds, induce neuronal differentiation in PC12 cells through activation of ERK1/2 signaling pathway.
pubmed:affiliation
Department of Longevity and Aging Research, Gifu International Institute of Biotechnology, 1-1 Naka-fudogaoka, Kakamigahara, Gifu 504-0838, Japan.
pubmed:publicationType
Journal Article