J Korean Med Sci.  2009 Feb;24(1):132-137. 10.3346/jkms.2009.24.1.132.

Proteomic Analysis of Rat Brains Following Exposure to Electroconvulsive Therapy

Affiliations
  • 1Department of Psychiatry, College of Medicine and Institute of Health Sciences, Gyeongsang National University, Jinju, Korea. bjkim@gnu.ac.kr
  • 2Department of Biochemistry, College of Medicine and Institute of Health Sciences, Gyeongsang National University, Jinju, Korea.
  • 3MRC for Neural Dysfunction, College of Medicine and Institute of Health Sciences, Gyeongsang National University, Jinju, Korea.

Abstract

Electroconvulsive therapy (ECT) is one of the most effective treatments used in psychiatry to date. The mechanisms of ECT action, however, are the least understood and still unclear. As a tool to elucidate the mechanisms of action of ECT, we employed proteomic analysis based on the identification of differentially expressed proteins after exposure to repeated ECT in rat brains. The expression of proteins was visualized by silver stain after two-dimensional gel electrophoresis. Of 24 differentially expressed protein spots (p<0.05 by Student t-test), six different proteins from 7 spots were identified by matrix-assisted laser desorption/ionization time-of flight (MALDI-TOF)/mass spectrometry. Among the identified proteins, there were five dominantly expressed proteins in the ECT-treated rat brain tissues (p<0.05); S100 protein beta chain, 14-3-3 protein zeta/delta, similar to ubiquitin-like 1 (sentrin) activating enzyme subunit 1, suppressor of G2 allele of SKP1 homolog, and phosphatidylinositol transfer protein alpha. The expression of only one protein, ACY1 protein, was repressed (p<0.05). These findings likely serve for a better understanding of mechanisms involved in the therapeutic effects of ECT.

Keyword

Proteomics; Electroconvulsive Therapy

MeSH Terms

Animals
Brain/*metabolism
*Electroconvulsive Therapy
Electrophoresis, Gel, Two-Dimensional
Proteome/*metabolism
Proteomics/methods
Rats
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Up-Regulation

Figure

  • Fig. 1 Two-dimensional gel electrophoresis patterns of proteins from the ECT-treated rat brain tissue (A) and normal control brain tissue (B). Proteins were identified using MALDI-TOF/mass spectrometry and peptide mass fingerprinting. Identified spots were indicated by numbers.

  • Fig. 2 Peptide mass fingerprinting of 14-3-3 protein zeta/delta. The spot P35213 was in-gel digested with trypsin. After desalting, the peptide mixture was analyzed by MALDI-TOF/mass spectrometry. The abscissa represents the mass/charge ratio of ions detected in the MALDI-TOF experiments. The ordinate denotes the relative intensity of the averaged ion current in arbitrary units. The peaks for trypsin and keratin were excluded.

  • Fig. 3 2-DE patterns showing up-regulated protein spots (A, indicated by arrowheads) and down-regulated spot (B, indicated by circle) in ECT-treated rat brain tissues (left panel) compared with control brain tissues (middle panel). The histogram in the right panel shows the relative intensities of protein spots expressed in ECT-treated (open bar) and control tissues (shaded bar). AVE, average.


Reference

1. Shergill SS, Katona CL. Helmchen H, Henn F, Lauter H, Sartorius N, editors. Pharmacotherapy of affective disorders. Contemporary Psychiatry. 2001. 4th ed. Heidelberg: Springer;317–336.
Article
2. Rohlff C. Proteomics in molecular medicine: applications in central nervous systems disorders. Electrophoresis. 2000. 21:1227–1234.
Article
3. Morrison RS, Kinoshita Y, Johnson MD, Conrads TP. Proteomics in the postgenomic age. Adv Protein Chem. 2003. 65:1–23.
Article
4. Moseley FL, Bicknell KA, Marber MS, Brooks G. The use of proteomics to identify novel therapeutic targets for the treatment of disease. J Pharm Pharmacol. 2007. 59:609–628.
Article
5. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976. 72:248–254.
Article
6. Görg A, Weiss W, Dunn MJ. Current two-dimensional electrophoresis technology for proteomics. Proteomics. 2004. 4:3665–3685.
Article
7. Hwa JS, Kim HJ, Goo BM, Park HJ, Kim CW, Chung KH, Park HC, Chang SH, Kim YW, Kim DR, Cho GJ, Choi WS, Kang KR. The expression of ketohexokinase is diminished in human clear cell type of renal cell carcinoma. Proteomics. 2006. 6:1077–1084.
Article
8. Donato R. S100: a multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular functional roles. Int J Biochem Cell Biol. 2001. 33:637–668.
Article
9. Rothermundt M, Falkai P, Ponath G, Abel S, Burkle H, Diedrich M, Hetzel G, Peters M, Siegmund A, Pedersen A, Maier W, Schramm J, Suslow T, Ohrmann P, Arolt V. Glial cell dysfunction in schizophrenia indicated by increased S100B in the CSF. Mol Psychiatry. 2004. 9:897–899.
Article
10. Busnello JV, Leke R, Oses JP, Feier G, Bruch R, Quevedo J, Kapczinski F, Souza DO, Cruz Portela LV. Acute and chronic electroconvulsive shock in rats: effects on peripheral markers of neuronal injury and glial activity. Life Sci. 2006. 78:3013–3017.
Article
11. Yaffe MB, Rittinger K, Volinia S, Caron PR, Aitken A, Leffers H, Gamblin SJ, Smerdon SJ, Cantley LC. The structural basis for 14-3-3: phosphopeptide binding specificity. Cell. 1997. 91:961–971.
12. Urschel S, Bassermann F, Bai RY, Munch S, Peschel C, Duyster J. Phosphorylation of Grb10 regulates its interaction with 14-3-3. J Biol Chem. 2005. 280:16987–16993.
Article
13. Bell R, Munro J, Russ C, Powell JF, Bruinvels A, Kerwin RW, Collier DA. Systematic screening of the 14-3-3 eta (n) chain gene for polymorphic variants and case-control analysis in schizophrenia. Am J Med Genet. 2000. 96:736–743.
14. Vawter MP, Barrett T, Cheadle C, Sokolov BP, Wood WH 3rd, Donovan DM, Webster M, Freed WJ, Becker KG. Application of cDNA microarrays to examine gene expression differences in schizophrenia. Brain Res Bull. 2001. 55:641–650.
Article
15. Wong AH, Macciardi F, Klempan T, Kawczynski W, Barr CL, Lakatoo S, Wong M, Buckle C, Trakalo J, Boffa E, Oak J, Azevedo MH, Dourado A, Coelho I, Macedo A, Vicente A, Valente J, Ferreira CP, Pato MT, Pato CN, Kennedy JL, Van Tol HH. Identification of candidate genes for psychosis in rat models, and possible association between schizophrenia and the 14-3-3eta gene. Mol Psychiatry. 2003. 8:156–166.
16. Middleton FA, Peng L, Lewis DA, Levitt P, Mirnics K. Altered expression of 14-3-3 genes in the prefrontal cortex of subjects with schizophrenia. Neuropsychopharmacology. 2005. 30:974–983.
Article
17. Thomas GM, Cunningham E, Fensome A, Ball A, Totty NF, Truong O, Hsuan JJ, Cockcroft S. An essential role for phosphatidylinositol transfer protein in phospholipase C-mediated inositol lipid signaling. Cell. 1993. 74:919–928.
Article
18. Kauffmann-Zeh A, Thomas GM, Ball A, Prosser S, Cunningham E, Cockcroft S, Hsuan JJ. Requirement for phosphatidylinositol transfer protein in epidermal growth factor signaling. Science. 1995. 268:1188–1190.
Article
19. Baraban JM. Toward a crystal-clear view of lithium's site of action. Proc Natl Acad Sci, USA. 1994. 91:5738–5739.
Article
20. Pollack SJ, Atack JR, Knowles MR, McAllister G, Ragan CI, Baker R, Fletcher SR, Iversen LL, Broughton HB. Mechanism of inositol monophosphatase, the putative target of lithium therapy. Proc Natl Acad Sci, USA. 1994. 91:5766–5770.
Article
21. Manji HK, Chen G, Hsiao JK, Risby ED, Masana MI, Potter WZ. Regulation of signal transduction pathways by mood-stabilizing agents: implications for the delayed onset of therapeutic efficacy. J Clin Psychiatry. 1996. 57:Suppl 13. 34–46.
22. Giardina T, Biagini A, Massey-Harroche D, Puigserver A. Distribution and subcellular localization of acylpeptide hydrolase and acylase I along the hog gastro-intestinal tract. Biochimie. 1999. 81:1049–1055.
Article
23. Lindner H, Hopfner S, Tafler-Naumann M, Miko M, Konrad L, Rohm KH. The distribution of aminoacylase I among mammalian species and localization of the enzyme in porcine kidney. Biochimie. 2000. 82:129–137.
Article
24. Cook RM, Franklin WA, Moore MD, Johnson BE, Miller YE. Mutational inactivation of aminoacylase-I in a small cell lung cancer cell line. Genes Chromosomes Cancer. 1998. 21:320–325.
Full Text Links
  • JKMS
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr