Potentiation of nerve growth factor-action by picrosides I and II, natural iridoids, in PC12D cells. 2000

P Li, and K Matsunaga, and T Yamakuni, and Y Ohizumi
Department of Pharmaceutical Molecular Biology, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Aramaki, Aoba-ku, 980-8578, Sendai, Japan.

Natural iridoid, picroside I (beta-D-glucopyranoside, 1a,1b,2,5a,6, 6a-hexahydro-6-hydroxy-1a-(hydroxymethyl)oxireno[4,5]cyclopenta[1, 2-c]pyran-2-yl, 6-(3-phenyl-2-propenoate)) or II (beta-D-glucopyranoside, 1a,1b,2,5a,6, 6a-hexahydro-6-[(4-hydroxy-3-methoxybenzoyl)oxy]-1a-(hydroxymethyl )ox ireno[4,5]cyclopenta[1,2-c]pyran-2-yl) alone did not exhibit neuritogenic activity, but caused a concentration-dependent (>0.1 microM) enhancement of nerve growth factor (NGF, 2 ng/ml)-induced neurite outgrowth from PC12D cells. The picroside-induced enhancing action of NGF was abolished by GF109203X (2-[1-(3-dimethylaminopropyl)-indol-3-yl]-3-(indol-3-yl)maleimide) (0.1 microM), a protein kinase C inhibitor. Furthermore, PD98059 (2-(2'-amino-3'-methoxyphenyl)-oxanaphthalen-4-one) (20 microM), a potent mitogen-activated protein (MAP) kinase kinase inhibitor, completely blocked the picroside-induced enhancement of neurite outgrowth in the presence of NGF (2 ng/ml), suggesting that picrosides activate the MAP kinase-dependent signaling pathway. Interestingly, no increase in the expression of phosphorylated MAP kinase was observed in picroside-treated (60 microM) PC12D cells in the presence of NGF (2 ng/ml). These results suggest that picroside I or II enhances NGF-induced neurite outgrowth from PC12D cells, probably by amplifying a down-stream step of MAP kinase in the NGF receptor-mediated intracellular MAP kinase-dependent signaling pathway.

UI MeSH Term Description Entries
D007211 Indoles Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
D008301 Maleimides Derivatives of maleimide (the structural formula H2C2(CO)2NH) containing a pyrroledione ring where the hydrogen atom of the NH group is replaced with aliphatic or aromatic groups.
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D002934 Cinnamates Derivatives of cinnamic acid (the structural formula: phenyl-HC Cinnamate
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D005419 Flavonoids A group of phenyl benzopyrans named for having structures like FLAVONES. 2-Phenyl-Benzopyran,2-Phenyl-Chromene,Bioflavonoid,Bioflavonoids,Flavonoid,2-Phenyl-Benzopyrans,2-Phenyl-Chromenes,2 Phenyl Benzopyran,2 Phenyl Benzopyrans,2 Phenyl Chromene,2 Phenyl Chromenes
D005960 Glucosides A GLYCOSIDE that is derived from GLUCOSE. Glucoside
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D016501 Neurites In tissue culture, hairlike projections of neurons stimulated by growth factors and other molecules. These projections may go on to form a branched tree of dendrites or a single axon or they may be reabsorbed at a later stage of development. "Neurite" may refer to any filamentous or pointed outgrowth of an embryonal or tissue-culture neural cell. Neurite
D016716 PC12 Cells A CELL LINE derived from a PHEOCHROMOCYTOMA of the rat ADRENAL MEDULLA. PC12 cells stop dividing and undergo terminal differentiation when treated with NERVE GROWTH FACTOR, making the line a useful model system for NERVE CELL differentiation. Pheochromocytoma Cell Line,Cell Line, Pheochromocytoma,Cell Lines, Pheochromocytoma,PC12 Cell,Pheochromocytoma Cell Lines

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