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Proteomics Technology Identifies The Differential Expression Proteins In Serum Between Guillain-Barré Syndrome And Normal

Posted on:2010-03-21Degree:MasterType:Thesis
Country:ChinaCandidate:R L ZhangFull Text:PDF
GTID:2144360275469906Subject:Neurology
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Object: Guillain-Barre syndrome (GBS) is an acute, inflammatory polyneuropathy that is caused by an immune response most commonly after an infection. The clinical presentation is characterised by progressive symmetrical paralysis of limbs with or without sensory and autonomic disturbances. The major pathology disorder of Guillain–Barrésyndrome (GBS) is inflammational segmental demyelination or axonal degeneration of nerve peripheralis, Because it involves in respiratory muscle paralysis, the fatality and disabled rate of GBS is high. Generally, GBS belongs to autoimmune disease. There are antibody, cytokines and complement in the blood of GBS. If we can know what they are, we will do a meaning thing in studying the pathogenesis of disease and overcoming the disease.The proteomics is a key area of research that is developing in the post-genome era. Proteomics is an ideal instrument that can compare protein level between different samples. Proteomics offers scientists the possibility of identifying disease-associated protein markers to assist in diagnosis or prognosis and to select potential targets for specific drug therapy.The majority of the capillaries direct exchange material and energy with human cells, So the changes of serum protein can reflect the majority of tissue pathological changes. Serum proteomics is the study of selected target groups in the expression of serum total protein, to establish the normal patterns of protein expression,in search of its different proteins, to identify the disease-related proteins, which are useful for us to comprehend the disease mechanisms.To deeply understand the molecule mechanism of GBS,the proteomics was employed to study the serum of GBS and normal.Methods: The serum of Guillain - Barre syndrome patients and normal human (both 30 examples) were obtained from the Department of Neurology, the second hospital affiliated Hebei Medical University. The serum proteins extracted with mixture of urea, CHAPS, DTT, IPG buffer and protease inhibitors were run immobilized pH gradient (IPG) isoelectric focusing electrophoresis as the first dimension, and then run vertical SDS-PAGE as the second dimension. The maps were visualized by colloidal coomassive blue R250 and analysised with ImageMaster 2D Elite software. The proteins of interest were digested and identified using MALDI-TOF mass spectrometry and MALDI-TOF/TOF tandem mass spectrometry. Results: All 24 protein spots were differentially expressed as compared with age-matched normal control serum, and 17 up-regulated proteins in GBS were identified as complement C3, Alpha-2-macroglobulin, Complement factor B, Ceruloplasmin, Complement factor H, Complement C4-B, Vitamin D-binding protein, Serum amyloid P component, Alpha-1-antichymotrypsin, Clusterin, Haptoglobin, Afamin, Hemopexin, Complement C1s subcomponent, Retinol-binding protein 4, Complement C4-A, Zinc-alpha-2-glycoprotein. 7 down-regulated proteins in GBS were identified as Alpha-1-antitrypsin, Ig gamma-1 chain C region, Ig kappa chain C region, Serotransferrin, CD5 antigen-like, ApolipoproteinE, Vitamin D-binding protein.Conclusions: Haptoglobin, a-1-antitrypsin, Alpha-1-antichymotrypsin, plasma ceruloplasmin, Serum amyloid P-component, Alpha-2-macroglobulin, Hemopexin and clusterin proteins are members of the acute phase protein, which are considered as pathological mechanism markers of obvious inflammation, tissue damage or malignant tumors. The above up-regulated proteins in GBS are probably a manifestation of acute inflammatory response. Complement are up-regulated, which further illustrates that the pathogenesis of GBS involve immune mechanismment. Apolipoprotein E is down-regulated in GBS patients, which prompts the repairation and regeneration of Schwann cell with GBS is in barriers to happen because of the down-regulated Apolipoprotein E, and then causes the results of peripheral nerve demyelination. Vitamin D-binding protein is an immune-regulating factor. The body will have autoimmune diseases if they are lack of Vitamin D-binding protein.We discover a set of differential expression protein by proteomics, which will helps us to deeply understand the pathogenesisof GBS and takes effect on early diagnosis and treatment of GBS.
Keywords/Search Tags:Proteomics, serum, two-dimensional gel Electrophoresis, GBS, the differrence protein
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