Metabolite 1 of protopanaxadiol-type saponins, an axonal regenerative factor, stimulates teneurin-2 linked by PI3-kinase cascade.

Abstract

We previously showed that 20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol (M1), a metabolite of protopanaxadiol-type ginseng saponins by intestinal bacteria had axonal extension activity in degenerated neurons, and improved memory disorder and synaptic loss induced by an active fragment of amyloid beta, Abeta(25-35). It is unknown how M1 shows these effects in neurons. To clarify the signal transduction mechanism of M1-induced axonal extension, phosphorylated proteins by M1 stimulation were identified because most cellular signal pathways are regulated by phosphorylation/dephosphorylation. The combination of immunoprecipitation and MALDI-TOF-MS revealed that teneurin-2 and mPar3 were specifically phosphorylated by M1 stimulation. Because mPar3 is known as an axonal specifying molecule and to be regulated by phosphatidylinositol 3-kinase (PI3-kinase), the involvement of teneurin-2 and PI3-kinase in the M1 signal was studied. In teneurin-2-deficient cortical neurons, M1-induced axonal extension and PI3-kinase activation were significantly inhibited. In addition, treatment with PI3-kinase inhibitor also reduced M1-induced axonal extension. These results suggest that M1 induces axonal outgrowth through the teneurin-2-PI3-kinase cascade.

• Authors: Chihiro Tohda, Itsuki Hashimoto, Tomoharu Kuboyama, Katsuko Komatsu
• Journal: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology (Neuropsychopharmacology) Vol. 31 Issue 6 Pg. 1158-64 (Jun 2006) ISSN: 0893-133X [Print] England
• PMID: 16292329 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Chromones
• Enzyme Inhibitors
• MAP2 protein, rat
• Membrane Proteins
• Microtubule-Associated Proteins
• Morpholines
• Peptides
• RNA, Small Interfering
• Sapogenins
• Triterpenes
• 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
• protopanaxadiol

Topics

• Amyloid beta-Peptides (toxicity)
• Animals
• Cells, Cultured
• Cerebral Cortex (cytology)
• Chromones (pharmacology)
• Dose-Response Relationship, Drug
• Embryo, Mammalian
• Enzyme Inhibitors (pharmacology)
• Immunohistochemistry (methods)
• Immunoprecipitation (methods)
• Membrane Proteins (metabolism)
• Microtubule-Associated Proteins (metabolism)
• Morpholines (pharmacology)
• Neurites (drug effects)
• Neurons (cytology, drug effects)
• Peptides (toxicity)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphorylation (drug effects)
• RNA, Small Interfering (metabolism)
• Rats
• Rats, Sprague-Dawley
• Reverse Transcriptase Polymerase Chain Reaction (methods)
• Sapogenins (pharmacology)
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization (methods)
• Transfection (methods)
• Triterpenes (pharmacology)