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Exp Clin Endocrinol Diabetes 2011; 119(5): 265-270
DOI: 10.1055/s-0031-1271705
Article

© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Proteome Analysis of Differential Protein Expression in Brain of Rats with Type 1 Diabetes Mellitus

X. Li1 , W. Pan1 , G. Z. Yang1 , Y. N. Di1 , F. Zhao1 , L. Y. Zhu1 , Z. H. Jiang1
  • 1Department of Medical Laboratory, Guiyang Medical College, Department of Clinical Biochemistry, Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou, P.R. China
Further Information

Publication History

received 26.11.2010 first decision 15.01.2011

accepted 19.01.2011

Publication Date:
06 April 2011 (online)

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Abstract

Aim of the study: Proteomic approach was applied to identify differential protein expressed in brain of rats with type 1 diabetes mellitus (T1DM) in order to search for potential biomarkers for pathological changes of brain with T1DM.

Methods: Proteins were extracted from brain tissues of T1DM rats and healthy control rats, separated by 2-DE and identified by MALDI-TOF-MS. The results were validated by Western blot analysis and immunohistochemistry (IHC).

Results: A total of 8 proteins from the 24 differentially expressed spots were identified by MALDI-TOF-MS. The proteins identified were vitamin D-dependent calcium-binding protein, creatine kinase B-type (B-CK), myosin light chain kinase (MLCK), HSP60 and HSP71, ATP synthase, cyclin-G, pantothenate kinase-1 (PANK1), respectively. 3 proteins were up-regulated and 5 proteins were down-regulated from the T1DM rats. Of the 8 proteins identified, MLCK was confirmed by Western blot and IHC.

Conclusion: This work demonstrates that a comprehensive strategy of proteomic identification should be a useful tool for understanding of diabetic encephalopathy mechanism. And the differential proteins such as MLCK may be give clues about the pathogenesis of diabetic encephalopathy.

Key words

proteome - type 1 diabetes mellitus - brain - streptozotocin

References

  • 1 Bao Y, Jiang L, Shi YQ. et al . Increased expression of phosphorylated Smad2 and Smad3 in the hippocampus of streptozotocin-induced diabetic rats.  Exp Clin Endocrinol Diabetes. 2010;  118 (1) 47-50 [PubMed: 19834880]
    Google Scholar
  • 2 Brands AM, Kessels RP, de Haan EH. et al . Cerebral dysfunction in type 1 diabetes: effects of insulin, vascular risk factors and blood glucose levels.  Eur J Pharmacol. 2004;  490 (1–3) 159-168 [PubMed: 15094082]
    Google Scholar
  • 3 Fazeli SA. Neuroprotection in diabetic encephalopathy.  Neurodegenerative Dis. 2009;  6 (5–6) 213-218 [PubMed: 20145418]
    Google Scholar
  • 4 Fountoulakis M. Application of proteomics technologies in the investigation of the brain.  Mass Spectrum Rev. 2004;  23 (4) 231-258 [PubMed: 15133836]
    Google Scholar
  • 5 Fountoulakis M, Kossida S. Proteomics-driven progress in neurodegeneration research.  Electrophoresis. 2006;  27 (8) 1556-1573 [PubMed: 16555340]
    Google Scholar
  • 6 He RX, Gu CL, Shen F. et al . Changes in expression of adrenomedullin in the myocardium of streptozotocin-induced diabetic rats.  Chin Med J. 2007;  120 (3) 187-191 [PubMed: 17355819]
    Google Scholar
  • 7 Huber JD, VanGilder RL, Houser KA. Streptozotocin-induced diabetes progressively increases blood-brain barrier permeability in specific brain regions in rats.  Am J Physiol Heart Circ Physiol. 2006;  291 (6) 2660-2668 [PubMed: 16951046]
    Google Scholar
  • 8 Jian X, Szaro BG, Schmidt JT. Myosin light chain kinase: expression in neurons and up-regulation during axon regeneration.  J Neurobiol. 1996;  31 (3) 567-578 [PubMed: 8910795]
    Google Scholar
  • 9 Li ZG, Sima AA. C-peptide and central nervous system complications in diabetes.  Exp Diabesity Res. 2004;  5 (1) 9-90 [PubMed: 15198373]
    Google Scholar
  • 10 Liang XC, Guo SS, Hagino N. Current status of clinical and experimental researches on cognitive impairment in diabetes.  Chin J Integr Med. 2006;  12 (1) 68-74 [PubMed: 16571291]
    Google Scholar
  • 11 Messier C. Impact of impaired glucose tolerance and type 2 diabetes on cognitive ageing.  Neurobiol Aging. 2005;  26 (suppl 1) 26-30 [PubMed: 16236384]
    Google Scholar
  • 12 Mochida S, Kobayashi H, Matsuda Y. et al . Myosin II is involved in transmitter release at synapses formed between rat sympathetic neurons in culture.  Neuron. 1994;  13 (5) 1331-1142 [PubMed: 7946350]
    Google Scholar
  • 13 Pandey A, Mann M. Proteomics to study genes and genomes.  Nature. 2000;  405 (6788) 837-846 [PubMed: 10866210]
    Google Scholar
  • 14 Pasquier F, Boulogne A, Leys D. et al . Diabetes mellitus and dementia.  Diabetes Metab. 2006;  32 (5Pt1) 403-414 [PubMed: 17110895]
    Google Scholar
  • 15 Rabilloud T. Two-dimensional gel electrophoresis in proteomics: Old, old fashioned, but it still climbs up the mountains.  Proteomics. 2002;  2 (1) 3-10 [PubMed: 11788986]
    Google Scholar
  • 16 Ryan TA. Inhibitors of myosin light chain kinase block synaptic vesicle pool mobiliztion during action potential firing.  J Neurosci. 1999;  19 (4) 1317-1323 [PubMed: 9952409]
    Google Scholar
  • 17 Sasaki N, Fukatsu R, Tsuzuki K. et al . Advanced glycation end products in Alzheimer's disease and other neurodegenerative disease.  Am J Pathol. 1998;  153 (4) 149-1155 [PubMed: 9777946]
    Google Scholar
  • 18 Stasyk T, Morandell S, Bakry R. et al . Quantitative detection of phosphoproteins by combination of two-dimensional difference gel electrophoresis and phosphospecific fluorescent staining.  Electrophoresis. 2005;  26 (14) 2850-2854 [PubMed: 15966015]
    Google Scholar
  • 19 Shin DH, Chun YS, Lee KH. et al . Arrest defective-1 controls tumor cell behavior by acetylating myosin light chain kinase.  PLoS One. 2009;  14 (4) e7451 [PubMed: 19826488]
    Google Scholar
  • 20 Sun Y, Zang Z, Xu X. et al . Differential proteomics identification of HSP90 as potential serum biomarker in hepatocellular carcinoma by two-dimensional electrophoresis and mass spectrometry.  Int J Mol Sci. 2010;  11 (4) 1423-1433 [PubMed: 20480028]
    Google Scholar
  • 21 van den Berg E, Reijmer YD, de Bresser J. et al . A 4 year follow-up study of cognitive functioning in patients with type 2 diabetes mellitus.  Diabetologia. 2010;  53 (1) 58-65 [PubMed: 19882137]
    Google Scholar
  • 22 Wang T, Fu FH, Han B. et al . Aspirin attenuates cerebral ischemic injury in diabetic rats.  Exp Clin Endocrinol Diabetes. 2009;  117 (4) 181-185 [PubMed: 9053022]
    Google Scholar
  • 23 Wild S, Roglic G, Green A. et al . Global prevalence of diabetes: estimates for the year 2000 and projections for 2030.  Diabetes Care. 2004;  27 (5) 1047-1053 [PubMed: 15111519]
    Google Scholar
  • 24 Xu L, Li B, Cheng M. et al . Oral administration of grape seed proanthocyanidin extracts down-regulate RAGE dependant nuclear factor-kappa BP65 expression in the hippocampus of streptozotocin induced Diabetic rats.  Exp Clin Endocrinol diabetes. 2008;  116 (4) 215-224 [PubMed: 18273752]
    Google Scholar
  • 25 Yang W, Lu J, Weng J. et al . Prevalence of diabetes among men and women in China.  N Engl J Med. 2010;  362 (12) 1090-1101 [PubMed: 20335585]
    Google Scholar
  • 26 Zhang XG, Yan H, Shen YL. et al . Decreased thrombospondin-I (TSP-I) expression in the hippocampus of streptozotocin-induced diabetic rats.  Exp Clin Endocrinol Diabetes. 2008;  116 (6) 309-314 [PubMed: 18700275]
    Google Scholar

Correspondence

W. PanMD 

Department of Medical

Laboratory

Guiyang Medical College

550004 Guiyang

Phone: +86 0851 6780726

Fax: +86 0851 6761424

Email: pw_6602@sina.com

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