Melia toosendan regulates PC12 Cell differentiation via the activation of protein kinase A and extracellular signal-regulated kinases.
With a history of several thousand years, traditional Chinese medicine has been well documented to be effective in the treatment of various disorders. We have investigated the activities of potential neuroactive compounds in traditional Chinese medicine such as Melia toosendan using an in vitro model system, rat pheochromocytoma PC12 cells. We report here that treatment of PC12 cells with a crude extract of the fruits of M. toosendan reduces cell growth in a dose-dependent manner without detectable cytotoxicity. Upon treatment with M. toosendan, PC12 cells exhibit robust neurite outgrowth, to a greater extent than that observed with nerve growth factor. Results obtained with specific kinase inhibitors and protein kinase A-deficient PC12 cells indicate that the actions of M. toosendan are mediated by the activation of protein kinase A and extracellular signal-regulated kinases.
Department of Biochemistry, Biotechnology Research Institute and Molecular Neuroscience Center, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
Jowie C H
JC
Yu
Zhi-Da
ZD
Min
Nancy Y
NY
Ip
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D019556:COS Cells / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase; D031585:Melia / Q000737:chemistry*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects; D016716:PC12 Cells; D051381:Rats; D020917:Receptor, trkA / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles; D013997:Time Factors; D014315:Triterpenes
D016895:Culture Media, Serum-Free; D017868:Cyclic AMP-Dependent Protein Kinases; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D007770:L-Lactate Dehydrogenase; D020928:Mitogen-Activated Protein Kinases; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D013778:Tetrazolium Salts; D013844:Thiazoles; C036454:toosendanin; D014315:Triterpenes; C022616:thiazolyl blue