Artepillin C derived from propolis induces neurite outgrowth in PC12m3 cells via ERK and p38 MAPK pathways.
We investigated whether artepillin C, a major component of Brazilian propolis, acts as a neurotrophic-like factor in rat PC12m3 cells, in which nerve growth factor (NGF)-induced neurite outgrowth is impaired. When cultures of PC12m3 cells were treated with artepillin C at a concentration of 20 microM, the frequency of neurite outgrowth induced by artepillin C was approximately 7-fold greater than that induced by NGF alone. Artepillin C induced-neurite outgrowth of PC12m3 cells was inhibited by the ERK inhibitor U0126 and by the p38 MAPK inhibitor SB203580. Although artepillin C-induced p38 MAPK activity was detected in PC12m3 cells, phosphorylation of ERK induced by artepillin C was not observed. On the other hand, artepillin C caused rapid activation of ERK and the time course of the activation was similar to that induced by NGF treatment in PC12 parental cells. However, NGF-induced neurite outgrowth was inhibited by artepillin C treatment. Interestingly, inhibition of ERK by U0126 completely prevented artepillin C-induced p38 MAPK phosphorylation of PC12m3 cells. These findings suggest that artepillin C-induced activation of p38 MAPK through the ERK signaling pathway is responsible for the neurite outgrowth of PC12m3 cells.
Kano
Yoshio
Y
Department of Occupational Therapy, School of Health Science, Kibi International University, 8 Iga-machi, Takahashi-city, Okayama, 716-8508, Japan. yoshio@kiui.ac.jp
Horie
Noboru
N
Doi
Shima
S
Aramaki
Fumika
F
Maeda
Hidefumi
H
Hiragami
Fukumi
F
Kawamura
Kenji
K
Motoda
Hirotoshi
H
Koike
Yoshihisa
Y
Akiyama
Junichi
J
Eguchi
Sueo
S
Hashimoto
Ken
K
D000470:Alkaloids / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D015394:Molecular Structure; D016501:Neurites / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D019384:Nucleic Acid Synthesis Inhibitors / Q000737:chemistry / Q000494:pharmacology; D016716:PC12 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010666:Phenylpropionates / Q000737:chemistry / Q000494:pharmacology*; D011429:Propolis / Q000737:chemistry* / Q000494:pharmacology; D011728:Pyridones / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D000470:Alkaloids; D000890:Anti-Infective Agents; D004791:Enzyme Inhibitors; D019384:Nucleic Acid Synthesis Inhibitors; D010666:Phenylpropionates; D011728:Pyridones; C449040:militarinone A; C102259:artepillin C; D011429:Propolis; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases