Potentiation of nerve growth factor-action by picrosides I and II, natural iridoids, in PC12D cells.
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.
Li
P
P
Department of Pharmaceutical Molecular Biology, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Aramaki, Aoba-ku, 980-8578, Sendai, Japan.
Matsunaga
K
K
Yamakuni
T
T
Ohizumi
Y
Y
D000818:Animals; D002934:Cinnamates / Q000494:pharmacology*; D004357:Drug Synergism; D005419:Flavonoids / Q000494:pharmacology; D005960:Glucosides / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D057888:Iridoid Glucosides; D008301:Maleimides / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D020932:Nerve Growth Factor / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D016716:PC12 Cells; D010766:Phosphorylation; D051381:Rats
D002934:Cinnamates; D005419:Flavonoids; D005960:Glucosides; D007211:Indoles; D057888:Iridoid Glucosides; D008301:Maleimides; C109270:picroside I; C416837:picroside II; D020932:Nerve Growth Factor; D020928:Mitogen-Activated Protein Kinases; C070515:bisindolylmaleimide I; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one