RRC ID 42941
著者 Kamata Y, Shiraga H, Tai A, Kawamoto Y, Gohda E.
タイトル Induction of neurite outgrowth in PC12 cells by the medium-chain fatty acid octanoic acid.
ジャーナル Neuroscience
Abstract It has been shown that polyunsaturated fatty acids such as arachinonic and docosahexanoic acids but not monounsaturated and saturated long-chain fatty acids promote basal and nerve growth factor (NGF)-induced neurite extension of PC12 cells, a line derived from a rat pheochromocytoma. On the other hand, short-chain fatty acids and valproic acid (2-propylpentanoic acid) enhance the growth of neurite processes of the cells only in the presence of inducers. In this study, we demonstrated that straight medium-chain fatty acids (MCFAs) at millimolar concentrations alone potently induced neuronal differentiation of PC12 cells. Hexanoic, heptanoic and octanoic acids dose-dependently induced neurite outgrowth of the cells: their maximal effects determined 2 days after addition to the culture medium were more marked than the effect of NGF. PC12 cells exposed to octanoic acid expressed increased levels of the neuronal marker beta-tubulin isotype III. Nonanoic, decanoic, and dodecanoic acids also induced growth of neurite processes, but their maximal effects were less marked than that of octanoic acid. In contrast, the polyunsaturated fatty acid linoleic acid and short-chain fatty acids had only slight or almost no effects on neurite formation in the absence of NGF. The effect of octanoic acid was synergistic with or additive to the effects of NGF and dibutyryl cyclic AMP. Octanoic acid upregulated phosphorylation of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK), critical signaling molecules in neuronal differentiation, but not phosphorylation of Akt, a signaling molecule downstream of phosphatidylinositol 3-kinase (PI3K). Moreover, growth of neurites induced by octanoic acid was potently inhibited by treatment of cells with the p38 MAPK inhibitor SB203580 and the ERK kinase inhibitor PD98059 but not inhibited and only slightly inhibited by the JNK inhibitor SP600125 and the PI3K inhibitor wortmannin, respectively. Taken together, our results indicate that MCFAs, including octanoic acid, induced neurite outgrowth of PC12 cells in the absence of NGF and suggest that the activation of p38 MAPK and ERK pathways is involved in this process.
巻・号 146(3)
ページ 1073-81
公開日 2007-5-25
DOI 10.1016/j.neuroscience.2007.03.001
PII S0306-4522(07)00308-9
PMID 17434686
MeSH Animals Blotting, Western Bucladesine / pharmacology Caproates / pharmacology Caprylates / pharmacology* Enzyme Activation / physiology Extracellular Signal-Regulated MAP Kinases / physiology Heptanoic Acids / pharmacology MAP Kinase Kinase 4 / metabolism Nerve Growth Factors / pharmacology Neurites / drug effects* PC12 Cells Phosphorylation Rats Tetrazolium Salts Thiazoles p38 Mitogen-Activated Protein Kinases / metabolism
IF 3.056
引用数 42
WOS 分野 NEUROSCIENCES
リソース情報
ヒト・動物細胞