Phenotyping of Tianma-Stimulated Differentiated Rat Neuronal B104 Cells by Quantitative ProteomicsSundaramurthi H.a · Manavalan A.a, b · Ramachandran U.a, b · Hu J.-M.c · Sze S.K.a · Heese K.a, b
aSchool of Biological Sciences, and bInstitute of Advanced Studies, Nanyang Technological University, Singapore; cKunming Institute of Botany, Chinese Academy of Science, Kunming, China
School of Biological Sciences, Department of Molecular and Cell Biology Nanyang Technological University, 60 Nanyang Drive
Singapore 637551 (Singapore)
Tel. +65 6316 2848, E-Mail Klaus.Heese@rub.de
Do you have an account?
Gastrodia elata blume (tianma) is a traditional Chinese herb often used in the treatment of convulsions, headaches, and hypertension. Although interest in neuronal-related actions of tianma is increasing, minimal studies have been conducted to determine its specific effects on neuronal cells. This study was designed to examine the effects of tianma on the metabolism in differentiated neuroblastoma cells using the isobaric tag for relative and absolute quantitation (iTRAQ) technology. Stimulation of these cells with tianma caused changes in the expression of 38 proteins that were subsequently classified according to their physiological functions and association with neurodegenerative diseases. We identified six proteins with altered functional activities in neurodegenerative disease states that were modulated by tianma: triosephosphate isomerase (Tpi1), peptidyl-prolyl cis-trans isomerase A (Ppia), neural cell adhesion molecule 1 (Ncam1), ubiquitin carboxyl-terminal hydrolase isozyme L1 (Uchl1), septin-2 (Sept2) and heat shock protein 90 (Hsp90aa1). We postulate that tianma mediates its neuroprotective effects via upregulation of Ncam1, Hsp90aa1, Tpi1 and Ppia while downregulating Sept2 and Uchl1. These changes in protein expression aid in the restoration of the intracellular environment to a metabolically balanced state, promoting cell survival. Based on these observed data, we conclude that tianma has therapeutic potential, especially for neurodegenerative diseases.
© 2011 S. Karger AG, Basel
- Taylor JP, Hardy J, Fischbeck KH: Toxic proteins in neurodegenerative disease. Science 2002;296:1991–1995.
- Soto C: Unfolding the role of protein misfolding in neurodegenerative diseases. Nat Rev Neurosci 2003;4:49–60.
- Rodolfo C, Ciccosanti F, Giacomo GD, Piacentini M, Fimia GM: Proteomic analysis of mitochondrial dysfunction in neurodegenerative diseases. Expert Rev Proteomics 2010;7:519–542.
- Hardy J, Orr H: The genetics of neurodegenerative diseases. J Neurochem 2006;97:1690–1699.
- Kokovay E, Shen Q, Temple S: The incredible elastic brain: how neural stem cells expand our minds. Neuron 2008;60:420–429.
- Forman MS, Trojanowski JQ, Lee VM: Neurodegenerative diseases: a decade of discoveries paves the way for therapeutic breakthroughs. Nat Med 2004;10:1055–1063.
- Prusiner SB: Shattuck lecture – neurodegenerative diseases and prions. N Engl J Med 2001;344:1516–1526.
- Shulman JM, De Jager PL: Evidence for a common pathway linking neurodegenerative diseases. Nat Genet 2009;41:1261–1262.
- Bulpitt CJ, Li Y, Bulpitt PF, Wang J: The use of orchids in Chinese medicine. JR Soc Med 2007;100:558–563.
- Kim HJ, Moon KD, Lee DS, Lee SH: Ethyl ether fraction of Gastrodia elata blume protects amyloid beta peptide-induced cell death. J Ethnopharmacol 2003;84:95–98.
- Huang NK, Chern Y, Fang JM, Lin CI, Chen WP, Lin YL: Neuroprotective principles from Gastrodia elata. J Nat Prod 2007;70:571–574.
- Ahn EK, Jeon HJ, Lim EJ, Jung HJ, Park EH: Anti-inflammatory and anti-angiogenic activities of Gastrodia elata blume. J Ethnopharmacol 2007;110:476–482.
- Ho SC, Ho YF, Lai TH, Liu TH, Su SY, Wu RY: Effect of tianma gouteng decoction with subtractive ingredients and its active constituents on memory acquisition. Am J Chin Med 2008;36:593–602.
- Kim HJ, Moon KD, Oh SY, Kim SP, Lee SR: Ether fraction of methanol extracts of Gastrodia elata, a traditional medicinal herb, protects against kainic acid-induced neuronal damage in the mouse hippocampus. Neurosci Lett 2001;314:65–68.
- Huang NK, Lin YL, Cheng JJ, Lai WL: Gastrodia elata prevents rat pheochromocytoma cells from serum-deprived apoptosis: the role of the MAPK family. Life Sci 2004;75:1649–1657.
- An H, Kim IS, Koppula S, Kim BW, Park PJ, Lim BO, Choi WS, Lee KH, Choi DK: Protective effects of Gastrodia elata blume on MPP+-induced cytotoxicity in human dopaminergic Sh-Sy5y cells. J Ethnopharmacol 2010;130:290–298.
- Mishra M, Huang J, Lee YY, See DKC, Lin X, Hu J-M, Heese K: Gastrodia elata modulates amyloid precursor protein cleavage and cognitive functions in mice. BioSci Trends 2011;5:129–138.
- Datta A, Park JE, Li X, Zhang H, Ho ZS, Heese K, Lim SK, Tam JP, Sze SK: Phenotyping of an in vitro model of ischemic penumbra by iTRAQ-based shotgun quantitative proteomics. J Proteome Res 2010;9:472–484.
- Encinas M, Iglesias M, Liu Y, Wang H, Muhaisen A, Cena V, Gallego C, Comella JX: Sequential treatment of Sh-Sy5Y cells with retinoic acid and brain-derived neurotrophic factor gives rise to fully differentiated, neurotrophic factor-dependent, human neuron-like cells. J Neurochem 2000;75:991–1003.
- Jamsa A, Hasslund K, Cowburn RF, Backstrom A, Vasange M: The retinoic acid and brain-derived neurotrophic factor differentiated Sh-Sy5y cell line as a model for Alzheimer’s disease-like tau phosphorylation. Biochem Biophys Res Commun 2004;319:993–1000.
- Ruiz-Leon Y, Pascual A: Induction of tyrosine kinase receptor B by retinoic acid allows brain-derived neurotrophic factor-induced amyloid precursor protein gene expression in human Sh-Sy5y neuroblastoma cells. Neuroscience 2003;120:1019–1026.
- Hiller K, Schobert M, Hundertmark C, Jahn D, Munch R: JVirGel: calculation of virtual two-dimensional protein gels. Nucleic Acids Res 2003;31:3862–3865.
- Ojemann LM, Nelson WL, Shin DS, Rowe AO, Buchanan RA: Tian ma, an ancient Chinese herb, offers new options for the treatment of epilepsy and other conditions. Epilepsy Behav 2006;8:376–383.
- Ahmed N, Battah S, Karachalias N, Babaei-Jadidi R, Horanyi M, Baroti K, Hollan S, Thornalley PJ: Increased formation of methylglyoxal and protein glycation, oxidation and nitrosation in triosephosphate isomerase deficiency. Biochim Biophys Acta 2003;1639:121–132.
- Gnerer JP, Kreber RA, Ganetzky B: Wasted away, a drosophila mutation in triosephosphate isomerase, causes paralysis, neurodegeneration, and early death. Proc Natl Acad Sci USA 2006;103:14987–14993.
- Park SA, Park HW, Kim NH, Kim YH, Kwak MJ, Shin JS, Kim CW: Effects of tau on the activity of triose phosphate isomerase (TPI) in brain cells. Neurochem Int 2010;56:886–892.
- Fanghanel J, Akiyama H, Uchida C, Uchida T: Comparative analysis of enzyme activities and mRNA levels of peptidyl prolyl cis/trans isomerases in various organs of wild type and pin1–/– mice. FEBS Lett 2006;580:3237–3245.
- Lu KP, Finn G, Lee TH, Nicholson LK: Prolyl cis-trans isomerization as a molecular timer. Nat Chem Biol 2007;3:619–629.
- Butterfield DA, Abdul HM, Opii W, Newman SF, Joshi G, Ansari MA, Sultana R: Pin1 in Alzheimer’s disease. J Neurochem 2006;98:1697–1706.
- Lu PJ, Wulf G, Zhou XZ, Davies P, Lu KP: The prolyl isomerase Pin1 restores the function of Alzheimer-associated phosphorylated tau protein. Nature 1999;399:784–788.
- Pastorino L, Sun A, Lu PJ, Zhou XZ, Balastik M, Finn G, Wulf G, Lim J, Li SH, Li X, Xia W, Nicholson LK, Lu KP: The prolyl isomerase Pin1 regulates amyloid precursor protein processing and amyloid-beta production. Nature 2006;440:528–534.
- Liou YC, Sun A, Ryo A, Zhou XZ, Yu ZX, Huang HK, Uchida T, Bronson R, Bing G, Li X, Hunter T, Lu KP: Role of the prolyl isomerase Pin1 in protecting against age-dependent neurodegeneration. Nature 2003;424:556–561.
- Balastik M, Lim J, Pastorino L, Lu KP: Pin1 in Alzheimer’s disease: multiple substrates, one regulatory mechanism? Biochim Biophys Acta 2007;1772:422–429.
- Luo GR, Chen S, Le WD: Are heat shock proteins therapeutic target for Parkinson’s disease? Int J Biol Sci 2007;3:20–26.
- Hartl FU, Hayer-Hartl M: Converging concepts of protein folding in vitro and in vivo. Nat Struct Mol Biol 2009;16:574–581.
- Dou F, Netzer WJ, Tanemura K, Li F, Hartl FU, Takashima A, Gouras GK, Greengard P, Xu H: Chaperones increase association of tau protein with microtubules. Proc Natl Acad Sci USA 2003;100:721–726.
- Ali YO, Kitay BM, Zhai RG: Dealing with misfolded proteins: examining the neuroprotective role of molecular chaperones in neurodegeneration. Molecules 2010;15:6859–6887.
- Uryu K, Richter-Landsberg C, Welch W, Sun E, Goldbaum O, Norris EH, Pham CT, Yazawa I, Hilburger K, Micsenyi M, Giasson BI, Bonini NM, Lee VM, Trojanowski JQ: Convergence of heat shock protein 90 with ubiquitin in filamentous alpha-synuclein inclusions of alpha-synucleinopathies. Am J Pathol 2006;168:947–961.
- Falsone SF, Kungl AJ, Rek A, Cappai R, Zangger K: The molecular chaperone hsp90 modulates intermediate steps of amyloid assembly of the Parkinson-related protein alpha-synuclein. J Biol Chem 2009;284:31190–31199.
- Dickey CA, Kamal A, Lundgren K, Klosak N, Bailey RM, Dunmore J, Ash P, Shoraka S, Zlatkovic J, Eckman CB, Patterson C, Dickson DW, Nahman NS Jr, Hutton M, Burrows F, Petrucelli L: The high-affinity hsp90-chip complex recognizes and selectively degrades phosphorylated tau client proteins. J Clin Invest 2007;117:648–658.
- Kang CB, Hong Y, Dhe-Paganon S, Yoon HS: Fkbp family proteins: immunophilins with versatile biological functions. Neurosignals 2008;16:318–325.
- Goryunov D, Liem RK: Chip-ping away at tau. J Clin Invest 2007;117:590–592.
- Pirkl F, Buchner J: Functional analysis of the hsp90-associated human peptidyl prolyl cis/trans isomerases fkbp51, fkbp52 and cyp40. J Mol Biol 2001;308:795–806.
- Carrello A, Allan RK, Morgan SL, Owen BA, Mok D, Ward BK, Minchin RF, Toft DO, Ratajczak T: Interaction of the hsp90 cochaperone cyclophilin 40 with hsc70. Cell Stress Chaperones 2004;9:167–181.
- Osaka H, Wang YL, Takada K, Takizawa S, Setsuie R, Li H, Sato Y, Nishikawa K, Sun YJ, Sakurai M, Harada T, Hara Y, Kimura I, Chiba S, Namikawa K, Kiyama H, Noda M, Aoki S, Wada K: Ubiquitin carboxy-terminal hydrolase L1 binds to and stabilizes monoubiquitin in neuron. Hum Mol Genet 2003;12:1945–1958.
- Gong B, Cao Z, Zheng P, Vitolo OV, Liu S, Staniszewski A, Moolman D, Zhang H, Shelanski M, Arancio O: Ubiquitin hydrolase Uch-L1 rescues beta-amyloid-induced decreases in synaptic function and contextual memory. Cell 2006;126:775–788.
- Setsuie R, Wada K: The functions of Uch-L1 and its relation to neurodegenerative diseases. Neurochem Int 2007;51:105–111.
- Barrachina M, Castano E, Dalfo E, Maes T, Buesa C, Ferrer I: Reduced ubiquitin c-terminal hydrolase-1 expression levels in dementia with Lewy bodies. Neurobiol Dis 2006;22:265–273.
- Hall PA, Russell SE: The pathobiology of the septin gene family. J Pathol 2004;204:489–505.
- Peterson EA, Petty EM: Conquering the complex world of human septins: implications for health and disease. Clin Genet 2010;77:511–524.
- Kinoshita A, Kinoshita M, Akiyama H, Tomimoto H, Akiguchi I, Kumar S, Noda M, Kimura J: Identification of septins in neurofibrillary tangles in Alzheimer’s disease. Am J Pathol 1998;153:1551–1560.
- Boutin C, Schmitz B, Cremer H, Diestel S: NCAM expression induces neurogenesis in vivo. Eur J Neurosci 2009;30:1209–1218.
- Jin K, Peel AL, Mao XO, Xie L, Cottrell BA, Henshall DC, Greenberg DA: Increased hippocampal neurogenesis in Alzheimer’s disease. Proc Natl Acad Sci USA 2004;101:343–347.
- Klementiev B, Novikova T, Novitskaya V, Walmod PS, Dmytriyeva O, Pakkenberg B, Berezin V, Bock E: A neural cell adhesion molecule-derived peptide reduces neuropathological signs and cognitive impairment induced by Abeta25–35. Neuroscience 2007;145:209–224.
- Neiiendam JL, Kohler LB, Christensen C, Li S, Pedersen MV, Ditlevsen DK, Kornum MK, Kiselyov VV, Berezin V, Bock E: An NCAM-derived FGF-receptor agonist, the FGL-peptide, induces neurite outgrowth and neuronal survival in primary rat neurons. J Neurochem 2004;91:920–935.
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.