Summary.
Mesial temporal lobe epilepsy (MTLE), the most common form of epilepsy, is characterised by cytoarchitectural abnormalities including neuronal cell loss and reactive gliosis in hippocampus. Determination of aberrant cytoskeleton protein expression by proteomics techniques may help to understand pathomechanism that is still elusive. We searched for differential expression of hippocampal proteins by an analytical method based on two-dimensional gel electrophoresis (2-DE) coupled with mass spectrometry unambiguously identifying 77 proteins analysed in eight control and eight MTLE hippocampi. Proteins were quantified and we observed 18 proteins that were altered in MTLE. Cytoskeleton proteins tubulin α-1 chain, β-tubulin, profilin II, neuronal tropomodulin were significantly reduced and one actin spot was missing, whereas ezrin and vinculin were significantly increased in MTLE. Proteins of several classes as e.g. antioxidant proteins (peroxiredoxins 3 and 6), chaperons (T-complex protein 1-α, stress-induced-phosphoprotein 1), signaling protein MAP kinase kinase 1, synaptosomal proteins (synaptotagmin I, α-synuclein), NAD-dependent deacetylase sirtuin-2 and 26S protease regulatory subunit 7 protein, neuronal-specific septin 3 were altered in MTLE. Taken together, the findings may represent or lead to cytoskeletal impairment; aberrant antioxidant proteins, chaperons, MAP kinase kinase 1 and NAD-dependent deacetylase sirtuin-2 may have been involved in pathogenetic mechanisms and altered synaptosomal protein expression possibly reflects synaptic impairment in MTLE.
Similar content being viewed by others
References
PW Baas (2002) ArticleTitleNeuronal polarity: microtubules strike back Nat Cell Biol 4 194–195 Occurrence Handle10.1038/ncb0802-e194 Occurrence Handle1:CAS:528:DC%2BD38Xls1Ort7o%3D
T Babb WJ Brown (1987) Pathological findings in epilepsy J Engel SuffixJr (Eds) Surgical treatment of epilepsies Raven Press New York 511–540
G Bernert M Fountoulakis G Lubec (2002) ArticleTitleManifold decreased protein levels of matrin 3, reduced motor protein HMP and hlark in fetal Down’s syndrome brain Proteomics 2 1752–1757 Occurrence Handle12469345 Occurrence Handle1:CAS:528:DC%2BD3sXht1Wmsg%3D%3D Occurrence Handle10.1002/1615-9861(200212)2:12<1752::AID-PROT1752>3.0.CO;2-Y
S Brady DR Colman P Brophy (2003) Subcellular organization of the nervous system: organelles and their functions LR Squire FE Bloom SK McConnell JL Roberts NC Spitzer MJ Zigmond (Eds) Fundamental neuroscience Academic Press San Diego 79–114
ME Brown PC Bridgman (2004) ArticleTitleMyosin function in nervous and sensory systems J Neurobiol 58 118–130 Occurrence Handle14598375 Occurrence Handle1:CAS:528:DC%2BD2cXlvVemug%3D%3D Occurrence Handle10.1002/neu.10285
CG Dos Remedios D Chhabra M Kekic IV Dedova M Tsubakihara DA Berry NJ Nosworthy (2003) ArticleTitleActin binding proteins: regulation of cytoskeletal microfilaments Physiol Rev 83 433–473 Occurrence Handle12663865 Occurrence Handle1:CAS:528:DC%2BD3sXjtVagtro%3D
SC Dryden FA Nahhas JE Nowak AS Goustin MA Tainsky (2003) ArticleTitleRole for human SIRT2 NAD-dependent deacetylase activity in control of mitotic exit in the cell cycle Mol Cell Biol 23 3173–3185 Occurrence Handle12697818 Occurrence Handle1:CAS:528:DC%2BD3sXjt1GlsL4%3D Occurrence Handle10.1128/MCB.23.9.3173-3185.2003
SK Dutcher (2001) ArticleTitleThe tubulin fraternity: alpha to eta Curr Opin Cell Biol 13 49–54 Occurrence Handle11163133 Occurrence Handle1:CAS:528:DC%2BD3MXht1KgsLc%3D Occurrence Handle10.1016/S0955-0674(00)00173-3
G Eitzen (2003) ArticleTitleActin remodeling to facilitate membrane fusion Biochim Biophys Acta 1641 175–181 Occurrence Handle12914958 Occurrence Handle1:CAS:528:DC%2BD3sXmt1Gru7o%3D Occurrence Handle10.1016/S0167-4889(03)00087-9
J Engel SuffixJr (1996) ArticleTitleIntroduction to temporal lobe epilepsy Epilepsy Res 26 141–150 Occurrence Handle8985696 Occurrence Handle10.1016/S0920-1211(96)00043-5
E Engidawork T Gulesserian M Fountoulakis G Lubec (2003) ArticleTitleAberrant protein expression in cerebral cortex of fetus with Down syndrome Neuroscience 122 145–154 Occurrence Handle14596856 Occurrence Handle1:CAS:528:DC%2BD3sXosVyhtbo%3D Occurrence Handle10.1016/S0306-4522(03)00605-5
E Engidawork G Lubec (2003) ArticleTitleMolecular changes in fetal Down syndrome brain J Neurochem 84 895–904 Occurrence Handle12603815 Occurrence Handle1:CAS:528:DC%2BD3sXit1ejtrk%3D Occurrence Handle10.1046/j.1471-4159.2003.01614.x
M Fountoulakis (2001) ArticleTitleProteomics: current technologies and applications in neurological disorders and toxicology Amino Acids 21 363–381 Occurrence Handle11858696 Occurrence Handle1:CAS:528:DC%2BD38XitVWitbc%3D Occurrence Handle10.1007/s007260170002
J Fujii Y Ikeda (2002) ArticleTitleAdvances in our understanding of peroxiredoxin, a multifunctional, mammalian redox protein Redox Rep 7 123–130 Occurrence Handle12189041 Occurrence Handle1:CAS:528:DC%2BD38Xmt1ahtrk%3D Occurrence Handle10.1179/135100002125000352
T Gulesserian SH Kim M Fountoulakis G Lubec (2002) ArticleTitleAberrant expression of centractin and capping proteins, integral constituents of the dynactin complex, in fetal down syndrome brain Biochem Biophys Res Commun 291 62–67 Occurrence Handle11829462 Occurrence Handle1:CAS:528:DC%2BD38Xpslygug%3D%3D Occurrence Handle10.1006/bbrc.2002.6389
JA Hadfield S Ducki N Hirst AT McGown (2003) ArticleTitleTubulin and microtubules as targets for anticancer drugs Prog Cell Cycle Res 5 309–325 Occurrence Handle14593726
H Hendriksen NA Datson WE Ghijsen EA van Vliet FH da Silva JA Gorter E Vreugdenhil (2001) ArticleTitleAltered hippocampal gene expression prior to the onset of spontaneous seizures in the rat post-status epilepticus model Eur J Neurosci 14 1475–1484 Occurrence Handle11722609 Occurrence Handle1:STN:280:DC%2BD3MnovFarsA%3D%3D Occurrence Handle10.1046/j.0953-816x.2001.01778.x
CA Hoeffer S Sanyal M Ramaswami (2003) ArticleTitleAcute induction of conserved synaptic signaling pathways in Drosophila melanogaster J Neurosci 23 6362–6372 Occurrence Handle12867522 Occurrence Handle1:CAS:528:DC%2BD3sXlvVCgsLs%3D
MM Horne TM Guadagno (2003) ArticleTitleA requirement for MAP kinase in the assembly and maintenance of the mitotic spindle J Cell Biol 161 1021–1028 Occurrence Handle12821640 Occurrence Handle1:CAS:528:DC%2BD3sXkvFCnu7g%3D Occurrence Handle10.1083/jcb.200304144
GD Jackson SF Berkovic JS Duncan A Connelly (1993) ArticleTitleOptimizing the diagnosis of hippocampal sclerosis using MR imaging Am J Neuroradiol 14 753–762 Occurrence Handle8517369 Occurrence Handle1:STN:280:DyaK3s3pslGnsQ%3D%3D
SH Kim M Fountoulakis NJ Cairns G Lubec (2002a) ArticleTitleHuman brain nucleoside diphosphate kinase activity is decreased in Alzheimer’s disease and Down syndrome Biochem Biophys Res Commun 296 970–975 Occurrence Handle1:CAS:528:DC%2BD38XmsV2rs7o%3D Occurrence Handle10.1016/S0006-291X(02)02035-1
SH Kim KS Shim G Lubec (2002b) ArticleTitleHuman brain nascent polypeptide-associated complex alpha subunit is decreased in patients with Alzheimer’s disease and Down syndrome J Investig Med 50 293–301 Occurrence Handle1:CAS:528:DC%2BD38Xls1Cht74%3D
K Krapfenbauer M Berger G Lubec M Fountoulakis (2001) ArticleTitleChanges in the brain protein levels following administration of kainic acid Electrophoresis 22 2086–2091 Occurrence Handle11465509 Occurrence Handle1:CAS:528:DC%2BD3MXltFamtrc%3D Occurrence Handle10.1002/1522-2683(200106)22:10<2086::AID-ELPS2086>3.0.CO;2-4
K Krapfenbauer E Engidawork N Cairns M Fountoulakis G Lubec (2003) ArticleTitleAberrant expression of peroxiredoxin subtypes in neurodegenerative disorders Brain Res 967 152–160 Occurrence Handle12650976 Occurrence Handle1:CAS:528:DC%2BD3sXitV2gsbc%3D Occurrence Handle10.1016/S0006-8993(02)04243-9
K Krapfenbauer BC Yoo M Fountoulakis E Mitrova G Lubec (2002) ArticleTitleExpression patterns of antioxidant proteins in brains of patients with sporadic Creutzfeldt-Jacob disease Electrophoresis 23 2541–2547 Occurrence Handle12210213 Occurrence Handle1:CAS:528:DC%2BD38XmsFOrsbg%3D Occurrence Handle10.1002/1522-2683(200208)23:15<2541::AID-ELPS2541>3.0.CO;2-1
E Little G Tocco M Baudry AS Lee SS Schreiber (1996) ArticleTitleInduction of glucose-regulated protein (glucose-regulated protein 78/BiP and glucose-regulated protein 94) and heat shock protein 70 transcripts in the immature rat brain following status epilepticus Neuroscience 75 209–219 Occurrence Handle8923535 Occurrence Handle1:CAS:528:DyaK28XmslGhu7Y%3D Occurrence Handle10.1016/0306-4522(96)00267-9
I Lopez C Ayala V Honrubia (2003) ArticleTitleSynaptophysin immunohistochemistry during vestibular hair cell recovery after gentamicin treatment Audiol Neurootol 8 80–90 Occurrence Handle12634456 Occurrence Handle1:CAS:528:DC%2BD3sXitFart7g%3D Occurrence Handle10.1159/000069001
B Lubec R Weitzdoerfer M Fountoulakis (2001) ArticleTitleManifold reduction of moesin in fetal Down syndrome brain Biochem Biophys Res Commun 286 1191–1194 Occurrence Handle11527426 Occurrence Handle1:CAS:528:DC%2BD3MXmtlejurk%3D Occurrence Handle10.1006/bbrc.2001.5520
K Lukasiuk L Kontula A Pitkanen (2003) ArticleTitlecDNA profiling of epileptogenesis in the rat brain Eur J Neurosci 17 271–279 Occurrence Handle12542663 Occurrence Handle10.1046/j.1460-9568.2003.02461.x
PJ Marangos DE Schmechel (1987) ArticleTitleNeuron specific enolase, a clinically useful marker for neurons and neuroendocrine cells Annu Rev Neurosci 10 269–295 Occurrence Handle3551759 Occurrence Handle1:CAS:528:DyaL2sXhslWmur8%3D Occurrence Handle10.1146/annurev.ne.10.030187.001413
SG Mueller AH Trabesinger P Boesiger HG Wieser (2001) ArticleTitleBrain glutathione levels in patients with epilepsy measured by in vivo (1)H-MRS Neurology 57 1422–1427 Occurrence Handle11673583 Occurrence Handle1:CAS:528:DC%2BD3MXot1Slu7c%3D
JV Nadler (2003) ArticleTitleThe recurrent mossy fiber pathway of the epileptic brain Neurochem Res 28 1649–1658 Occurrence Handle14584819 Occurrence Handle1:CAS:528:DC%2BD3sXnvFaltbc%3D Occurrence Handle10.1023/A:1026004904199
BJ North BL Marshall MT Borra JM Denu E Verdin (2003) ArticleTitleThe human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase Mol Cell 11 437–444 Occurrence Handle12620231 Occurrence Handle1:CAS:528:DC%2BD3sXit1Wgs7c%3D Occurrence Handle10.1016/S1097-2765(03)00038-8
D Pollak N Cairns G Lubec (2003) ArticleTitleCytoskeleton derangement in brain of patients with Down syndrome, Alzheimer’s disease and Pick’s disease J Neural Transm Suppl 67 139–148
H Pollard M Khrestchatisky J Moreau Y Ben-Ari A Represa (1994) ArticleTitleCorrelation between reactive sprouting and microtubule protein expression in epileptic hippocampus Neuroscience 61 773–787 Occurrence Handle7838377 Occurrence Handle1:STN:280:DyaK2M7ktVamug%3D%3D Occurrence Handle10.1016/0306-4522(94)90401-4
KE Poskanzer KW Marek ST Sweeney GW Davis (2003) ArticleTitleSynaptotagmin I is necessary for compensatory synaptic vesicle endocytosis in vivo Nature 426 559–563 Occurrence Handle14634669 Occurrence Handle1:CAS:528:DC%2BD3sXpsVejtrY%3D Occurrence Handle10.1038/nature02184
SA Reeves LJ Helman A Allison MA Israel (1989) ArticleTitleMolecular cloning and primary structure of human glial fibrillary acidic protein Proc Natl Acad Sci USA 86 5178–5182 Occurrence Handle2740350 Occurrence Handle1:CAS:528:DyaK3cXhslehtLg%3D Occurrence Handle10.1073/pnas.86.13.5178
A Represa H Pollard J Moreau G Ghilini M Khrestchatisky Y Ben-Ari (1993) ArticleTitleMossy fiber sprouting in epileptic rats is associated with a transient increased expression of alpha-tubulin Neurosci Lett 156 149–152 Occurrence Handle8414177 Occurrence Handle1:CAS:528:DyaK3sXlslyksrw%3D Occurrence Handle10.1016/0304-3940(93)90460-3
K Sato K Abe (2001) ArticleTitleIncreases in mRNA levels for Talpha1-tubulin in the rat kindling model of epilepsy Brain Res 904 157–160 Occurrence Handle11516424 Occurrence Handle1:CAS:528:DC%2BD3MXksVylur8%3D Occurrence Handle10.1016/S0006-8993(01)02459-3
E Schuller T Gulesserian R Seidl N Cairns G Lubec (2001) ArticleTitleBrain t-complex polypeptide 1 (TCP-1) related to its natural substrate beta1 tubulin is decreased in Alzheimer’s disease Life Sci 69 263–270 Occurrence Handle11441917 Occurrence Handle1:CAS:528:DC%2BD3MXktlOku7o%3D Occurrence Handle10.1016/S0024-3205(01)01126-2
AK Shetty V Zaman GA Shetty (2003) ArticleTitleHippocampal neurotrophin levels in a kainate model of temporal lobe epilepsy: a lack of correlation between brain-derived neurotrophic factor content and progression of aberrant dentate mossy fiber sprouting J Neurochem 87 147–159 Occurrence Handle12969262 Occurrence Handle1:CAS:528:DC%2BD3sXotFSksbc%3D Occurrence Handle10.1046/j.1471-4159.2003.01979.x
KS Shim G Lubec (2002) ArticleTitleDrebrin, a dendritic spine protein, is manifold decreased in brains of patients with Alzheimer’s disease and Down syndrome Neurosci Lett 324 209–212 Occurrence Handle12009525 Occurrence Handle1:CAS:528:DC%2BD38XjsFyhurs%3D Occurrence Handle10.1016/S0304-3940(02)00210-0
D Suckau A Resemann M Schuerenberg P Hufnagel J Franzen A Holle (2003) ArticleTitleA novel MALDI LIFT-TOF/TOF mass spectrometer for proteomics Anal Bioanal Chem 376 952–965 Occurrence Handle12830354 Occurrence Handle1:CAS:528:DC%2BD3sXmtVGrsr8%3D Occurrence Handle10.1007/s00216-003-2057-0
MA Sussman S Sakhi G Tocco I Najm M Baudry L Kedes SS Schreiber (1994) ArticleTitleNeural tropomodulin: developmental expression and effect of seizure activity Brain Res Dev Brain Res 80 45–53 Occurrence Handle7955359 Occurrence Handle1:CAS:528:DyaK2cXlsFeqt7c%3D Occurrence Handle10.1016/0165-3806(94)90088-4
M Takehashi T Alioto T Stedeford AS Persad M Banasik E Masliah S Tanaka K Ueda (2004) ArticleTitleSeptin 3 gene polymorphism in Alzheimer’s disease Gene Expr 11 263–270 Occurrence Handle15200238
G Tocco X Bi L Vician IK Lim H Herschman M Baudry (1996) ArticleTitleTwo synaptotagmin genes, Syt1 and Syt4, are differentially regulated in adult brain and during postnatal development following kainic acid-induced seizures Brain Res Mol Brain Res 40 229–239 Occurrence Handle8872307 Occurrence Handle1:CAS:528:DyaK28XkvFWkuro%3D Occurrence Handle10.1016/0169-328X(96)00055-1
R Vlkolinsky N Cairns M Fountoulakis G Lubec (2001) ArticleTitleDecreased brain levels of 2′,3′-cyclic nucleotide-3′-phosphodiesterase in Down syndrome and Alzheimer’s disease Neurobiol Aging 22 547–553 Occurrence Handle11445254 Occurrence Handle1:CAS:528:DC%2BD3MXltVCqtrg%3D Occurrence Handle10.1016/S0197-4580(01)00218-4
X Wang SA Phelan K Forsman-Semb EF Taylor C Petros A Brown CP Lerner B Paigen (2003) ArticleTitleMice with targeted mutation of peroxiredoxin 6 develop normally but are susceptible to oxidative stress J Biol Chem 278 25179–25190 Occurrence Handle12732627 Occurrence Handle1:CAS:528:DC%2BD3sXltVSlt7s%3D Occurrence Handle10.1074/jbc.M302706200
R Weitzdoerfer M Fountoulakis G Lubec (2002) ArticleTitleReduction of actin-related protein complex 2/3 in fetal Down syndrome brain Biochem Biophys Res Commun 293 836–841 Occurrence Handle12054546 Occurrence Handle1:CAS:528:DC%2BD38XksVGhtbY%3D Occurrence Handle10.1016/S0006-291X(02)00291-7
T Yamamoto C Toyoda M Kobayashi E Kondo K Saito M Osawa (1997) ArticleTitlePial-glial barrier abnormalities in fetuses with Fukuyama congenital muscular dystrophy Brain Dev 19 35–42 Occurrence Handle9071488 Occurrence Handle1:STN:280:DyaK2s3isFWitw%3D%3D Occurrence Handle10.1016/S0387-7604(96)00056-3
JW Yang T Czech G Lubec (2004) ArticleTitleProteomic profiling of human hippocampus Electrophoresis 25 1169–1174 Occurrence Handle15095461 Occurrence Handle1:CAS:528:DC%2BD2cXjvVartLo%3D Occurrence Handle10.1002/elps.200305809
JW Yang R Rodrigo V Felipo G Lubec (2005) ArticleTitleProteome analysis of primary neurons and astrocytes from rat cerebellum J Proteome Res 4 768–788 Occurrence Handle15952724 Occurrence Handle1:CAS:528:DC%2BD2MXktF2ks74%3D Occurrence Handle10.1021/pr049774v
MA Yenari (2002) ArticleTitleHeat shock proteins and neuroprotection Adv Exp Med Biol 513 281–299 Occurrence Handle12575825 Occurrence Handle1:CAS:528:DC%2BD3sXotlymsL0%3D
BC Yoo SH Kim N Cairns M Fountoulakis G Lubec (2001a) ArticleTitleDeranged expression of molecular chaperones in brains of patients with Alzheimer’s disease Biochem Biophys Res Commun 280 249–258 Occurrence Handle1:CAS:528:DC%2BD3MXivVeksg%3D%3D Occurrence Handle10.1006/bbrc.2000.4109
BC Yoo R Vlkolinsky E Engidawork N Cairns M Fountoulakis G Lubec (2001b) ArticleTitleDifferential expression of molecular chaperones in brain of patients with Down syndrome Electrophoresis 22 1233–1241 Occurrence Handle1:CAS:528:DC%2BD3MXjslWhs7g%3D Occurrence Handle10.1002/1522-2683()22:6<1233::AID-ELPS1233>3.0.CO;2-M
H Zhu C Zhu J Hao X Meng L Wang D Chen (2000) ArticleTitleScreening of novel epilepsy-related genes and isolation and identification of cDNAs J Tongji Med Univ 20 10–12 Occurrence Handle12845744 Occurrence Handle1:CAS:528:DC%2BD3cXmtlOjsbs%3D Occurrence Handle10.1007/BF02887663
Author information
Authors and Affiliations
Additional information
J. W. Yang and T. Czech have equally contributed to the paper.
Rights and permissions
About this article
Cite this article
Yang, J., Czech, T., Felizardo, M. et al. Aberrant expression of cytoskeleton proteins in hippocampus from patients with mesial temporal lobe epilepsy. Amino Acids 30, 477–493 (2006). https://doi.org/10.1007/s00726-005-0281-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00726-005-0281-y