Biomedical subjects

G Lubec

Publications and source records attributed to G Lubec.

At least 109 records · Page 6Linked to original sources

PubMed2001

Effect of intravenous iron supplementation on erythropoiesis in erythropoietin-treated premature infants.

OBJECTIVE: To test the efficacy and safety of combining intravenous iron in amounts approximating the in utero iron accretion rate and the postnatal iron loss with erythropoietin (EPO) in very low birth weight (VLBW) infants. METHODS: A prospective, controlled, randomized, unmasked trial lasting 21 days was performed in 29 clinically stable VLBW infants <31 weeks' gestation and <1300 g birth weight not treated with red blood cell transfusions during the study period. Mean (+/- standard error of the mean) age at study entry was 23 +/- 2.9 days. After a 3-day run-in baseline period in which all participants received oral supplements of 9 mg/kg/day of iron polymaltose complex (IPC), participants were randomized to receive 18 days of treatment with: 1) oral IPC alone (oral iron group); 2) 300 U of recombinant human EPO (r-HuEPO) kg/day and daily oral IPC (EPO + oral iron group); 3) 2 mg/kg/day of intravenous iron sucrose, r-HuEPO, and oral iron (intravenous iron + EPO group). To assess efficacy of the 3 treatments, serial blood samples were analyzed for hemoglobin (Hb), hematocrit (Hct), reticulocyte count, red blood cell indices and plasma levels of transferrin, transferrin receptor (TfR), ferritin, and iron. Oxidant injury was assessed before and after treatment by plasma and urine levels of malondialdehyde (MDA) and o-tyrosine. RESULTS: At the end of treatment, Hb, Hct, reticulocyte count, and plasma TfR were markedly higher in both of the EPO-treated groups, compared with the oral iron group. At study exit a trend toward increasing Hb and Hct levels and significantly higher reticulocyte counts were observed in the intravenous iron + EPO group, compared with the EPO + oral iron group. During treatment, plasma ferritin levels increased significantly in the intravenous iron + EPO group and decreased significantly in the other 2 groups. By the end of treatment, ferritin levels were significantly higher in the intravenous iron + EPO group compared with the other 2 groups. Although plasma and urine MDA or o-tyrosine did not differ among the 3 groups, plasma MDA was significantly greater in the subgroup of intravenous iron + EPO participants sampled at the end of the 2-hour parenteral iron infusion, compared with values observed immediately before and after parenteral iron-dosing. CONCLUSIONS: In stable VLBW infants receiving EPO treatment, parenteral supplementation with 2 mg/kg/day of iron sucrose results in a small, but significant, augmentation of erythropoiesis beyond that of r-HuEPO and enteral iron alone. However, to reduce the potential adverse effects of parenteral iron/kg/day on increasing plasma ferritin levels and on causing oxidative injury, we suggest that the parenteral iron dose used should be reduced and/or the time of infusion extended to maintain a serum iron concentration below the total iron-binding capacity.

Administration, Oral↗

PubMed2001

Superoxide dismutase SOD1, encoded on chromosome 21, but not SOD2 is overexpressed in brains of patients with Down syndrome.

BACKGROUND: The antioxidant enzyme Cu/Zn-superoxide dismutase-1 (SOD1) gene is localized to chromosome 21q22.1 and catalyzes the dismutation of superoxide anions to hydrogen peroxide, which may lead to the increased production of active oxygen species in Down Syndrome (DS), trisomy 21. Although a number of studies have addressed this question, proposing the overexpression hypothesis, no specific protein-chemical data on SOD protein levels in the brains of patients with DS are available. METHODS: We therefore determined the protein SOD-1 and SOD-2 levels in the brains of controls (n = 9) and adult patients with DS (n = 9) and Alzheimer disease (AD; n = 9). Two-dimensional electrophoresis followed by matrix-assisted laser desorption/ionization-mass spectroscopy detection and identification was used for the analyses. RESULTS: We found significantly increased SOD-1 levels in DS temporal, parietal, and occipital cortex, whereas SOD-1 was decreased in the AD temporal cortex and SOD-2 was comparable between all groups. CONCLUSIONS: Increased SOD-1 levels in patients with DS may reflect the overexpression by the trisomic state, as a response to the oxidative stress, as has been proposed in DS by several authors. However, it well may be that glial proliferation, which is markedly increased in DS brain, may underlie the increased brain levels of this ubiquitous protein. The decrease of SOD1 in the temporal cortex of patients with AD may reflect an antiapoptotic mechanism or simply cell loss in the brain.

Aged↗

PubMed2000

Increased protein levels of serotonin transporter in frontal cortex of patients with Down syndrome.

Serotonin transporters (SERTs) are presynaptic proteins specialized for the clearance of serotonin from the synaptic cleft. A large body of evidence exists on altered platelet serotonin uptake and metabolism in Down syndrome (DS). Besides, dysregulation of SERTs expression have been reported in various complex behavioural traits and disorders including, neurodegenerative disorders. This prompted us to investigate SERT protein levels in adult brain specimens. Western blot analyses were performed in frontal cortex and cerebellum of aged controls and patients with DS and Alzheimer's disease (AD). The result revealed that frontal cortex SERT was significantly increased (P<0.05) in DS, whereas in AD it was comparable to controls. In cerebellum, no significant difference was observed among the study populations. A remarkable difference was noted when SERT was normalized vs. neuron specific enolase (NSE), a neuronal marker. The increase in SERT/NSE was highly significant (P<0.01) in DS frontal cortex compared to controls. Neither AD frontal cortex nor DS and AD cerebellum did show any significant difference. These findings indicate that a region specific alteration in SERT expression may exist in DS with AD-like pathology. As little is known about the status of serotenergic synaptic markers in DS brain, the findings may contribute to an effort made to delineate the underlying causes of serotonergic dysfunction in DS and the quest for therapeutic strategies. The study also suggest caution should be taken in applying data obtained from DS to model AD biochemical defects.

Adult↗

PubMed2000

Effects of transdermal nicotine on cognitive performance in Down's syndrome.

Down's syndrome involves age-dependent neuropathological and neurochemical changes similar to Alzheimer's disease, with cholinergic deficits being the most consistent. There is currently no proven treatment for Down's syndrome. We investigated the effect of nicotine-agonistic stimulation with 5 mg transdermal patches, compared with placebo, on cognitive performance in five adults with the disorder. Improvements possibly related to attention and information processing were seen for Down's syndrome patients compared with healthy controls. Our preliminary findings are encouraging, although not generalizable because of small numbers.

Administration, Cutaneous↗

PubMed2000

Neuroendocrine-specific protein C, a marker of neuronal differentiation, is reduced in brain of patients with Down syndrome and Alzheimer's disease.

Neuroendocrine-specific protein C (NSP-C) is found in neural and neuroendocrine cells and associated with the endoplasmic reticulum. Its expression was found to correlate with the degree of neuronal differentiation. As the neuropathological findings in Down syndrome (DS) includes deficits of differentiation, and we detected a downregulated sequence with 100% homology with NSP-C homolog mRNA in temporal cortex of patients with DS as well as Alzheimer's disease (AD) using differential display-polymerase chain reaction (DD-PCR), we decided to examine the protein levels of NSP-C in temporal, frontal cortex and cerebellum of DS and AD. To normalize NSP-C versus neuronal density, we also determined neuron-specific enolase (NSE) levels and calculated the ratios. NSP-C was significantly reduced in DS (temporal and frontal cortex) and AD (frontal cortex) compared to controls. The significant decrease of NSP-C in DS was even more pronounced when related to NSE levels. Impaired differentiation in DS brain may well be due to absolutely and relatively decreased NSP-C levels in temporal and frontal cortex. As NSP-C was also reduced in AD frontal cortex, NSP-C deficits in these disorders may be reflecting neurodegenerative changes rather than a primary and specific finding of DS or AD pathogenesis.

Alzheimer Disease↗

PubMed2000

Energy metabolism in graded perinatal asphyxia of the rat.

Although information on energy metabolism during hypoxemic-ischemic states is abundant, data on perinatal asphyxia (PA) are limited. As results from hypoxia-ischemia cannot be directly extrapolated to PA, a clinical entity characterized by acidosis, hypoxemia and hypercapnia, we decided to use a rat model of graded PA during delivery. Cesarean section was performed at the 21st day of gestation and the pups, still in the uterus horns, were asphyxiated from 0 to 20 minutes. In this model survival decreases with the length of asphyxia. Early changes of energy-rich phosphates in brain, heart and kidney were determined by HPLC. ATP and phosphocreatine gradually decreased with the length of asphyxia, with highest ATP depletion rate occurring in the kidney. ATP: brain 1.39 +/- 0.71 (0 min) to 0.06 microM/g wwt (20 min); heart 4.73 +/- 0.34 (0 min) to 1.08 +/- 0.47 (20 min); kidney 1.62 +/- 0.11 (0 min) to 0.02 +/- 0.02 (20 min). Phosphocreatine: brain 1.65 +/- 0.68 (0 min) to 0.51 +/- 0.45 microM/g (20 min); heart 6.98 +/- 0.38 (0 min) to 6.17 +/- 1.07 (20 min); kidney 8.23 +/- 0.86 (0 min) to 3.76 +/- 0.54 (20 min). We present data on energy derangement in a rat model of PA, closely resembling the clinical situation, showing that energy depletion precedes cell damage and death.

Adenine Nucleotides↗

PubMed2000

Differences in protein level between neonatal and adult brain.

Age is a physiological condition that affects protein expression. We investigated differences in protein level between newborn and adult brains. Brain tissue extracts from male and female adult and neonatal rats were analyzed by two-dimensional gel electrophoresis. Gel comparison revealed the presence of many differences, of qualitative and quantitative nature, between a neonatal and adult brain. The most significant age-related difference concerned alpha-fetoprotein, which was detected in the brain of neonatal rats only. The levels of 22 proteins, including dihydropyrimidinase-related proteins 1,3, and 4 and 14-3-3 proteins, were higher in the neonatal brain, whereas the levels of 28 proteins, including dihydropyrimidinase-related protein 2, dynamin-1 and many enzymes were higher in the adult brain. We did not detect a consistent sex-related difference in the brain proteins. An inconsistency was observed in the location of the spot representing glial fibrillary acidic protein in the male brain.

Aging↗

PubMed2000

Brain RNA polymerase and nucleolar structure in perinatal asphyxia of the rat.

Ribosomes are integral constitutens of the protein synthesis machinery. Polymerase I (POL I) is located in the nucleolus and transcribes the large ribosomal genes. POL I activity is decreased in ischemia but nothing is known so far on POL I in perinatal asphyxia. We investigated the involvement of POL I in a well-documented model of graded systemic asphyxia at the level of activity, mRNA, protein, and morphology. Caeserean section was performed at the 21st day of gestation. Rat pups still in the uterus horns were immerged in a water bath for asphyctic periods from 5-20 min. Brain was taken for measurement of pH, nuclear POL I activity, and mRNA steady state, and protein levels of RPA40, an essential subunit of POL I and III. Silver staining and transmission electron microscopy with morphometry when appropriate were used to examine the nucleolus. Brain pH and nuclear POL I activity decreased with the length of the asphyctic period while POL-I mRNA and protein levels were unchanged. Accompanying the decrease in brain pH we found significant changes of nucleolar structure in the course of perinatal asphyxia at the light and electron microscopic level. As early as ten min following the asphyctic insult, morphological disintegration of the nucleolus was observed. The changes became more dramatic with longer duration of perinatal asphyxia. We conclude that severe acidosis may be responsible for decreased POL activity and for disintegration of nucleoli in neurons. This condition may lower the ribosome content in neonatal neurons and impair protein synthesis.

Animals↗

PubMed2000

Decreased levels of complex III core protein 1 and complex V beta chain in brains from patients with Alzheimer's disease and Down syndrome.

Ubiquinol:cytochrome c oxidoreductase (complex III) and ATP synthase (complex V) are important enzymes in the mitochondrial electron transport chain. Defects in mitochondrial respiratory enzymes have been reported for several neurodegenerative diseases. In this study, we applied the proteomic approach to investigate protein levels of complex III core protein and complex V beta chain in brain regions of Alzheimer's disease (AD) and Down syndrome (DS) patients. Complex III core protein 1 was significantly reduced in the temporal cortex of AD patients. Complex V beta chain was significantly reduced in the frontal cortex of DS patients. We conclude that decreased mitochondrial respiratory enzymes could contribute to the impairment of energy metabolism observed in DS. These decreases could also cause the generation of reactive oxygen species and neuronal cell death (apoptosis) in DS as well as AD.

Adenosine Triphosphatases↗

PubMed2000

Long term neurological and behavioral effects of graded perinatal asphyxia in the rat.

Perinatal hypoxic-ischemic states can cause irreversible damage to the brain, ranging from minimal brain dysfunction to death. Only few studies have been reported describing neurological, cognitive and behavioral deficits following perinatal asphyxia. We therefore decided to study long term effects of perinatal asphyxia in a well-documented animal model resembling the clinical situation. Caeserean section in rats was performed and the pups, still in the uterus horns, were placed into a water bath at 37 degrees C for periods of 5-20 min; pups were then given to surrogate mothers and examined at three month of age. Examinations consisted of a battery of motor and reflex tests, Morris water maze, multiple T-maze, elevated plus maze and open field studies. No abnormalities were found in rats even with long periods of perinatal asphyxia by neurological examination, in the open field and in mazes. Interestingly, in the elevated plus maze rats with long lasting exposure to hypoxia (15 and 20 min of asphyxia) showed reduced anxiety-related behavior. This finding may be relevant for the explanation of anxiety related disorders in adulthood with a tentative history in the perinatal period.

Animals↗

PubMed2000

The effect of repeated ozone exposures on inflammatory markers in bronchoalveolar lavage fluid and mucosal biopsies.

The aim of this study was to investigate the cellular and biochemical events associated with repeated exposures to ozone. Twenty-three healthy subjects underwent single exposures to 200 ppb ozone and to filtered air (FA), as well as repeated exposures to 200 ppb ozone on 4 consecutive days, each for 4 h of intermittent exercise. Bronchoalveolar lavage was performed and mucosal biopsies were taken 20 h after the single or the last of the repeated exposures. As compared with FA, the single exposure to ozone caused a decrease in FEV(1), an increase in the percentages of neutrophils and lymphocytes, the concentrations of total protein, IL-6, IL-8, reduced glutathione, urate, and ortho-tyrosine in BAL fluid (BALF), but no changes in the cellular composition of biopsy. After the repeated exposure, the effect on lung function was abolished and differential cell counts in BALF were not significantly different from those after FA. However, the concentrations of total protein, IL-6, IL-8, reduced glutathione, and ortho-tyrosine were still increased. IL-10 could only be detected in BALF after repeated ozone exposures. Furthermore, macroscopic scores for bronchitis, erythema, and hypervulnerability of airway mucosa were increased, as well as numbers of neutrophils in bronchial mucosal biopsies. Our data demonstrate that airway inflammation persists after repeated ozone exposure, despite attenuation of some inflammatory markers in BALF and adaptation of lung function.

Adult↗

PubMed2000

Glucose transporters, hexokinase, and phosphofructokinase in brain of rats with perinatal asphyxia.

Transport by glucose transporters from blood to the brain during hypoxic-ischemic conditions is well studied. However, the recent availability of a clinically related animal model of perinatal asphyxia and the fact that no concomitant determination of glucose transporters, parameters for glucose utilization, brain glucose, and cerebral blood flow (CBF) have been reported and the early phase of perinatal asphyxia has never been studied led us to perform the following study. Cesarean section was performed on full-term pregnant rats. The obtained pups within patent uterus horns were placed into a water bath at 37 degrees C from which they were subsequently removed after 5-20 min of graded asphyxia. Brain pH, brain tissue glucose, CBF, mRNA and activity of hexokinase and phosphofructokinase, and mRNA and protein of the glucose transporters GLUTI and GLUT3 were determined. Brain pH decreased and brain tissue glucose and CBF increased with the length of the asphyctic period; hexokinase and phosphofructokinase mRNA and activity were unchanged during the observation period. The mRNA and protein of both glucose transporters were comparable between normoxic and asphyctic groups. We show that glucose transport and utilization are unchanged in the early phase of perinatal asphyxia at a time point when CBF and brain glucose are already significantly increased and severe acidosis is present.

Animals↗

PubMed1999

Cholinergic, monoaminergic and glutamatergic changes following perinatal asphyxia in the rat.

Perinatal asphyxia (PA) is considered to lead to a variety of brain disorders including spasticity, epilepsy, mental retardation, and minimal brain disorder syndromes and may form the basis for psychiatric and neurodegenerative diseases later in life. We examined markers for neuronal transmission involved in the pathomechanisms of PA and candidates as mediators for long-term sequelae. We tested tyrosine hydroxylase (TH) and the vesicular monoamine transporter (VMAT) representing the monoaminergic system, the vesicular acetylcholine transporter (VAChT), and the excitatory amino acid carrier 1 (EAAC1), a neuronal subtype of the glutamate transporter, using immunohistochemistry on brain sections of rats subjected to graded PA. Three months following the asphyxiant insult immunoreactive (IR)-TH was decreased in striatum, hippocampus, thalamus, frontal cortex, and cerebellum; IR-VMAT was increased, and IR-VAChT was decreased in striatum. IR-EAAC1 glutamate transporter was increased in frontal cortex. The cholinergic, monoaminergic, and glutamatergic changes, still observed 3 months after the asphyxiant insult, may reflect their involvement in the pathomechanisms of PA and indicate mechanisms leading to long-term complications of PA. The variable consequences on the individual markers in several brain regions may be explained by specific susceptibility of cholinergic, monoaminergic, and glutamatergic neurons to the asphyxiant insult.

Age Factors↗

PubMed1999

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

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.

Aged↗

PubMed1999

Documenting the diet in ancient human populations through stable isotope analysis of hair.

Fundamental to the understanding of human history is the ability to make interpretations based on artefacts and other remains which are used to gather information about an ancient population. Sequestered in the organic matrices of these remains can be information, for example, concerning incidence of disease, genetic defects and diet. Stable isotopic compositions, especially those made on isolates of collagen from bones, have been used to help suggest principal dietary components. A significant problem in the use of collagen is its long-term stability, and the possibility of isotopic alteration during early diagenesis, or through contaminating condensation reactions. In this study, we suggest that a commonly overlooked material, human hair, may represent an ideal material to be used in addressing human diets of ancient civilizations. Through the analysis of the amino-acid composition of modern hair, as well as samples that were subjected to radiation (thus simulating ageing of the hair) and hair from humans that is up to 5200 years old, we have observed little in the way of chemical change. The principal amino acids observed in all of these samples are essentially identical in relative abundances and content. Dominating the compositions are serine, glutamic acid, threonine, glycine and leucine, respectively accounting for approximately 15%, 17%, 10%, 8% and 8% of the total hydrolysable amino acids. Even minor components (for example, alanine, valine, isoleucine) show similar constancy between the samples of different ages. This constancy clearly indicates minimal alteration of the amino-acid composition of the hair. Further, it would indicate that hair is well preserved and is amenable to isotopic analysis as a tool for distinguishing sources of nutrition. Based on this observation, we have isotopically characterized modern individuals for whom the diet has been documented. Both stable nitrogen and carbon isotope compositions were assessed, and together provide an indication of trophic status, and principal type (C3 or C4) of vegetation consumed. True vegans have nitrogen isotope compositions of about 7/1000 whereas humans consuming larger amounts of meat, eggs, or milk are more enriched in the heavy nitrogen isotope. We have also analysed large cross-sections of modern humans from North America and Europe to provide an indication of the variability seen in a population (the supermarket diet). There is a wide diversity in both carbon and nitrogen isotope values based at least partially on the levels of seafood, corn-fed beef and grains in the diets. Following analysis of the ancient hair, we have observed similar trends in certain ancient populations. For example, the Coptics of Egypt (1000 BP) and Chinchorro of Chile (5000-800 BP) have diets of similar diversity to those observed in the modern group but were isotopically influenced by local nutritional sources. In other ancient hair (Egyptian Late Middle Kingdom mummies, ca. 4000 BP), we have observed a much more uniform isotopic signature, indicating a more constant diet. We have also recognized a primary vegetarian component in the diet of the Neolithic Ice Man of the Oetztaler Alps (5200 BP). In certain cases, it appears that sulphur isotopes may help to further constrain dietary interpretations, owing to the good preservation and sulphur content of hair. It appears that analysis of the often-overlooked hair in archaeological sites may represent a significant new approach for understanding ancient human communities.

Amino Acids↗

PubMed1999

Apoptosis-associated proteins p53 and APO-1/Fas (CD95) in brains of adult patients with Down syndrome.

In Down syndrome (DS), enhanced apoptosis (programmed cell death) may play a role in the pathogenesis of characteristic mental retardation and precocious dementia of Alzheimer-type. Upregulation of p53 and APO-1/Fas (CD95) precedes apoptosis in many cell types, and a potential role for these molecules has already been demonstrated in Alzheimer's disease (AD) and several other neurodegenerative diseases. We measured p53 and APO-1/Fas (CD95) protein in four different regions of cerebral cortex and cerebellum in nine adult DS patients with Alzheimer-like neuropathologic lesions compared to nine controls. Quantitative ELISA demonstrated higher frontal lobe (mean+/-SD: 0.10+0.035 vs. 0.041+/-0.016 ng/mg protein), temporal lobe (0.062+/-0.021 vs. 0.032+/-0.019 ng/mg protein) and cerebellar levels (0.078+/-0.030 vs. 0.039+/-0.032 ng/mg protein) of p53 protein, and higher temporal lobe (mean+/-SD: 12.3+/-4.3 vs. 5.3+/-2.0 U/mg protein) and cerebellar levels (5.9+/-1.4 vs. 2.9+/-1.1 U/mg protein) of APO-1/Fas (CD95) protein. The results suggest that p53- or APO-1/Fas (CD95)-associated apoptosis may be an important feature of neurodegeneration in DS.

Adult↗

PubMed1999

Evidence against the current hypothesis of "gene dosage effects" of trisomy 21: ets-2, encoded on chromosome 21" is not overexpressed in hearts of patients with Down Syndrome.

BACKGROUND: The major current concept for the pathogenesis of the Down Syndrome (DS) phenotype including congenital heart disease (CHD) is the so-called "gene dosage effect." According to this hypothesis, genes encoded by chromosome 21 at the "critical region" (which is thought to be crucial for the development of the DS phenotype) are overexpressed in the trisomic state, thus leading to an imbalance of genes as, e.g., the protooncogene ets-2, superoxide dismutase, etc. METHODS: We studied heart biopsies obtained at surgery from 6 patients with DS and 7 patients with congenital heart disease. ets-2-mRNA steady state levels were determined by a competitive reverse transcription-polymerase chain reaction (RT-PCR) technique which allowed the determination of this gene at the attomol level. RESULTS: ets-2 mRNA in total ventricular tissue of DS patients showed concentrations of 0.60 +/- 0.42 fg/10 ng total RNA (mean, +/- SD). When normalized versus the housekeeping gene beta-actin to rule out general transcriptional changes in that disorder, the ratio of 0.56 +/- 0.28 (mean, +/- SD) was calculated. ets-2 mRNA in total ventricular tissue of patients with non-DS CHD showed concentrations of 0.45 +/- 0.22 fg/10 ng total RNA (mean, +/-SD) and ratios of 0.48 +/- 0.35 (mean, +/-SD). No differences could be found at the p<0.05 level. CONCLUSION: No absolute quantification of a gene incriminated in the "gene dosage effect-hypothesis" was performed so far and the only approach to (semi-) quantitative determination of the ets-2 gene using northern blotting was published on one individual DS sample only. This is the first report to clearly show that no overexpression of ets-2 can be found in heart of patients with DS, thus providing evidence against the current gene dosage effect-hypothesis.

Chromosome Mapping↗

PubMed1999

Enrichment of human brain proteins by heparin chromatography.

Detection of low-abundance proteins is essential for the identification of novel drug targets by differential protein expression studies. We studied the enrichment of human fetal brain proteins by heparin chromatography. Total soluble brain proteins were fractionated on Heparin-Actigel and the fractions collected were analyzed by two-dimensional electrophoresis. The proteins were identified by matrix-assisted laser desorption ionization mass spectrometry. Approximately 300 protein spots were analyzed, representing 70 different polypeptides, 50 of which were bound to the heparin matrix. Eighteen brain proteins were identified for the first time. The proteins enriched by heparin chromatography include both minor and major components of the brain protein extract. The enriched proteins belong to several classes, including proteasome components, dihydropirimidinase-related proteins, T-complex protein 1 components and enzymes with various catalytic activities. The results include a two-dimensional map of the soluble brain proteins and a list of the proteins enriched by heparin chromatography. These may be useful in the design of protein purification protocols and in studies of neurological disorders.

Brain Chemistry↗