J. Lipid Res. Neurobiology of Lipids (ISSN1683-5506)
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Originally published In Press as doi:10.1194/jlr.M600045-JLR200 on April 13, 2006

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Journal of Lipid Research, Vol. 47, 1434-1443, July 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Lysophosphatidylethanolamine in Grifola frondosa as a neurotrophic activator via activation of MAPK

Atsuyoshi Nishina1,*, Hirokazu Kimura{dagger}, Akihiro Sekiguchi*, Ryo-hei Fukumoto*, Satoshi Nakajima§ and Shoei Furukawa**

* Gunma Industrial Technology Center, 884-1 Kamesato, Maebashi, Gunma 379-2147, Japan
{dagger} Gunma Prefectural Institute of Public Health and Environmental Sciences, 378 Kamioki, Maebashi, Gunma 371-0052, Japan
§ Gunma National Collage of Technology, 580 Toribane, Maebashi, Gunma 371-530, Japan
** Laboratory of Molecular Biology, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585, Japan

Published, JLR Papers in Press, April 13, 2006.

1 To whom correspondence should be addressed. e-mail: nishina{at}tec-lab.pref.gunma.jp

We found that Grifola frondosa extracts induced the activation of mitogen-activated protein kinase (MAPK) in cultured PC12 cells, a line of rat pheochromocytoma cells. The active substance was isolated by a few chromatographic steps, including high-performance liquid chromatography, and was identified to be lysophosphatidylethanolamine (LPE) from various structural analyses. LPE from G. frondosa (GLPE) was confirmed to induce the activation of MAPK of cultured PC12 cells and was found to suppress cell condensation and DNA ladder generation evoked by serum deprivation, suggesting that the GLPE had antiapoptotic effects. Moreover, GLPE caused morphological changes in and upregulation of neurofilament M expression of PC12 cells, demonstrating that the GLPE could induce neuronal differentiation of these cells. The activation of MAPK by GLPE was suppressed by AG1478, an antagonist of epidermal growth factor receptor (EGFR), and by U0126, an inhibitor of MAPK kinase (MEK1/2), but not by K252a, an inhibitor of TrkA, or by pertussis toxin. These results demonstrate that GLPE induced the MAPK cascade [EGFR-MEK1/2-extracellular signal-regulated protein kinases (ERK1/2)] of PC12 cells, the activation of which induced neuronal differentiation and suppressed serum deprivation-induced apoptosis. This study has clarified for the first time the involvement of the MAPK signal cascade in LPE actions.

Supplementary key words mitogen-activated protein kinase signal cascade • neurofilament M • PC12 cells • epidermal growth factor receptor • U0126 • K252a • TrkA • pertussis toxin


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