IL-1β induced protein changes in diabetes prone BB rat islets of Langerhans identified by proteome analysis

被引:61
作者
Sparre, T
Christensen, UB
Larsen, PM
Fey, SJ
Wrzesinski, K
Roepstorff, P
Mandrup-Poulsen, T
Pociot, F
Karlsen, AE
Nerup, J
机构
[1] Steno Diabet Ctr, DK-2820 Gentofte, Denmark
[2] Ctr Proteome Anal, Odense, Denmark
[3] Univ So Denmark, Inst Biochem & Mol Biol, Odense, Denmark
关键词
proteome analysis; two dimensional gel; electrophoresis; mass spectrometry; cytokines; IL-1; beta; BB rat; diabetes; pathogenesis;
D O I
10.1007/s00125-002-0953-z
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Aims/hypothesis: Type I (insulin-dependent) diabetes mellitus is characterized by selective destruction of tire insulin producing beta cells. Interleukin-1beta (IL-1beta) modulates the beta-cell function, protein synthesis, energy production and cases apoptosis. We have previously shown changes in the expression of 82 out of 1 815 protein spots detected by two dimensional gel. electrophoresis in IL-1beta exposed diabetes prone Bio Breeding (BB-DP) rat islets of Langerhans in vitro. The aim of this study was to identify the proteins in these 82 spots by mass spectrometry and compare these changes with those seen in IL-1beta exposed Wistar Furth (WF) rat islets. Methods. The 82 protein spots, that changed expression after IL-1beta exposure, were all re-identified on preparative gels of 200 000 neonatal WF rat isle, cut out and subjected to mass spectrometry for identification. Results. Forty-five different proteins were identified from 51 spots and grouped according to function: (i) energy transduction and redox potentials; (ii) glycolytic and Krebs cycle enzymes; (iii) protein, DNA and RNA synthesis, chaperoning and protein folding; (iv) signal transduction, regulation, differentiation and apoptosis; (v) cellular defence; and (vi) other functions. Comparison of IL-1beta exposed BB-DP and WF islets showed common changes in 14 proteins and several proteins influencing similar pathways, suggesting that similar routes in the two strains lead to beta-cell destruction. Conclusion/interpretation. We demonstrate that proteome analysis is a powerful tool to identify proteins and pathways in BB-DP rat islets exposed to IL-1beta.
引用
收藏
页码:1550 / 1561
页数:12
相关论文
共 96 条
[51]   Proteome analysis of interleukin-1β-induced changes in protein expression in rat islets of Langerhans [J].
Larsen, PM ;
Fey, SJ ;
Larsen, MR ;
Nawrocki, A ;
Andersen, HU ;
Kähler, H ;
Heilmann, C ;
Voss, MC ;
Roepstorff, P ;
Pociot, F ;
Karlsen, AE ;
Nerup, J .
DIABETES, 2001, 50 (05) :1056-1063
[52]   Protection of insulin-producing RINm5F cells against cytokine-mediated toxicity through overexpression of antioxidant enzymes [J].
Lortz, S ;
Tiedge, M ;
Nachtwey, T ;
Karlsen, AE ;
Nerup, J ;
Lenzen, S .
DIABETES, 2000, 49 (07) :1123-1130
[53]   DECREASED EXPRESSION OF MAC-2 (CARBOHYDRATE BINDING PROTEIN-35) AND LOSS OF ITS NUCLEAR-LOCALIZATION ARE ASSOCIATED WITH THE NEOPLASTIC PROGRESSION OF COLON-CARCINOMA [J].
LOTZ, MM ;
ANDREWS, CW ;
KORZELIUS, CA ;
LEE, EC ;
STEELE, GD ;
CLARKE, A ;
MERCURIO, AM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (08) :3466-3470
[54]  
MANDRUPPOULSEN T, 1986, DIABETOLOGIA, V29, P63, DOI 10.1007/BF02427283
[55]   The role of interleukin-1 in the pathogenesis of IDDM [J].
MandrupPoulsen, T .
DIABETOLOGIA, 1996, 39 (09) :1005-1029
[56]   USE OF MASS-SPECTROMETRIC MOLECULAR-WEIGHT INFORMATION TO IDENTIFY PROTEINS IN SEQUENCE DATABASES [J].
MANN, M ;
HOJRUP, P ;
ROEPSTORFF, P .
BIOLOGICAL MASS SPECTROMETRY, 1993, 22 (06) :338-345
[57]   GLUTATHIONE [J].
MEISTER, A ;
ANDERSON, ME .
ANNUAL REVIEW OF BIOCHEMISTRY, 1983, 52 :711-760
[58]  
Miklos GLG, 2001, PROTEOMICS, V1, P169, DOI 10.1002/1615-9861(200102)1:2<169::AID-PROT169>3.0.CO
[59]  
2-C
[60]  
MINTURN JE, 1995, J NEUROSCI, V15, P6757