Lysophosphatidylethanolamine in Grifola frondosa as a neurotrophic activator via activation of MAPK.
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.
Nishina
Atsuyoshi
A
Gunma Industrial Technology Center, 884-1 Kamesato, Maebashi, Gunma 379-2147, Japan. nishina@tec-lab.pref.gunma.jp
Kimura
Hirokazu
H
Sekiguchi
Akihiro
A
Fukumoto
Ryo-hei
RH
Nakajima
Satoshi
S
Furukawa
Shoei
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D016895:Culture Media, Serum-Free; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000037:antagonists & inhibitors; D048691:Grifola / Q000737:chemistry*; D008246:Lysophospholipids / Q000302:isolation & purification* / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D009414:Nerve Growth Factors / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000494:pharmacology; D016716:PC12 Cells; D011799:Quinazolines; D051381:Rats; D020032:Tyrphostins / Q000494:pharmacology
D016895:Culture Media, Serum-Free; D008246:Lysophospholipids; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D011799:Quinazolines; D020032:Tyrphostins; C008301:lysophosphatidylethanolamine; C101044:RTKI cpd; D066246:ErbB Receptors; D019206:GTP-Binding Protein alpha Subunits, Gi-Go