Increased glyceraldehyde 3-phosphate dehydrogenase levels in the brain of patients with Down's syndrome

被引:32
作者
Lubec, G
Labudova, O
Cairns, N
Fountoulakis, M
机构
[1] F Hoffmann La Roche, Pharmaceut Res Gene Technol, CH-4070 Basel, Switzerland
[2] Univ Vienna, Dept Pediat, Vienna, Austria
[3] Brain Bank, Inst Psychiat, London, England
关键词
Down's syndrome; glyceraldehyde 3-phosphate dehydrogenase; brain; two-dimensional gel electrophoresis; subtractive hybridization; Alzheimer's disease;
D O I
10.1016/S0304-3940(98)00952-5
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Impaired glucose metabolism in Down's syndrome (DS) has been well-documented in vivo, although information on the underlying biochemical defect is limited and no biochemical studies on glucose handling enzymes have been carried out in the brain. In a previous study, we found by gene hunting in DS brain an overexpressed sequence homologous to the glyceraldehyde 3-phosphate dehydrogenase (G3PD) gene. Here we studied G3PD activity and expression levels, using two-dimensional gel analysis, in five brain regions of patients with DS and Alzheimer's disease (AD). The protein expression levels in four brain areas were approximately 1.5-fold higher in patients with DS in comparison with the controls. G3PD activity was significantly elevated in the frontal, parietal, occipital and temporal lobe of DS as well, but not in the corresponding AD brain regions. We conclude that our biochemical findings complement previously published data of impaired brain glucose metabolism in DS evaluated by positron emission tomography in clinical studies. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:141 / 145
页数:5
相关论文
共 20 条
[1]   INSULIN STIMULATES GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE GENE-EXPRESSION THROUGH CIS-ACTING DNA-SEQUENCES [J].
ALEXANDER, MC ;
LOMANTO, M ;
NASRIN, N ;
RAMAIKA, C .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (14) :5092-5096
[2]  
ANNEREN KG, 1987, HUM GENET, V76, P63
[3]  
BEUTLER E, RED CELL METABOLISM, P51
[4]  
BURGER PC, 1973, AM J PATHOL, V73, P457
[5]  
EPSTEIN CJ, 1992, METABOLIC MOL BASIS, P749
[6]   Identification of proteins by matrix-assisted laser desorption ionization mass spectrometry following in-gel digestion in low-salt, nonvolatile buffer and simplified peptide recovery [J].
Fountoulakis, M ;
Langen, H .
ANALYTICAL BIOCHEMISTRY, 1997, 250 (02) :153-156
[7]   LUTEINIZING-HORMONE-RELEASING HORMONE-RECEPTOR MESSENGER-RIBONUCLEIC-ACID EXPRESSION IN THE RAT PITUITARY DURING LACTATION AND THE ESTROUS-CYCLE [J].
FUNABASHI, T ;
BROOKS, PJ ;
WEESNER, GD ;
PFAFF, DW .
JOURNAL OF NEUROENDOCRINOLOGY, 1994, 6 (03) :261-266
[8]   VARIATION IN EXPRESSION OF GENES USED FOR NORMALIZATION OF NORTHERN BLOTS AFTER INDUCTION OF CELL-PROLIFERATION [J].
GOLDSWORTHY, SM ;
GOLDSWORTHY, TL ;
SPRANKLE, CS ;
BUTTERWORTH, BE .
CELL PROLIFERATION, 1993, 26 (06) :511-518
[9]   cAMP upregulates the transposable element mys-1: A possible link between signaling and mobile DNA [J].
Labudova, O ;
Lubec, G .
LIFE SCIENCES, 1997, 62 (05) :431-437
[10]   Effect of protein application mode and acrylamide concentration on the resolution of protein spots separated by two-dimensional gel electrophoresis [J].
Langen, H ;
Roder, D ;
Juranville, JF ;
Fountoulakis, M .
ELECTROPHORESIS, 1997, 18 (11) :2085-2090