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Biomedical subjects

Martin H Maurer

Publications and source records attributed to Martin H Maurer.

At least 19 recordsLinked to original sources
PubMed2006

Adult neural stem cells express glucose transporters GLUT1 and GLUT3 and regulate GLUT3 expression.

In the brain, glucose is transported by GLUT1 across the blood-brain barrier and into astrocytes, and by GLUT3 into neurons. In the present study, the expression of GLUT1 and GLUT3 mRNA and protein was determined in adult neural stem cells cultured from the subventricular zone of rats. Both mRNAs and proteins were coexpressed, GLUT1 protein being 5-fold higher than GLUT3. Stress induced by hypoxia and/or hyperglycemia increased the expression of GLUT1 and GLUT3 mRNA and of GLUT3 protein. It is concluded that adult neural stem cells can transport glucose by GLUT1 and GLUT3 and can regulate their glucose transporter densities.

Animals↗
PubMed2006

Reduced cerebral blood flow but elevated cerebral glucose metabolic rate in erythropoietin overexpressing transgenic mice with excessive erythrocytosis.

To examine the impact of excessive erythrocytosis on local cerebral blood flow (CBF) and cerebral glucose metabolic rate (CMR(glc)), we made use of our constitutively erythropoietin (Epo)-overexpressing transgenic mouse line (tg-6) that reach a mean hematocrit of 0.87. Compared with wild-type (wt) control siblings, CBF decreased by 44% in tg-6 mice, while upon hemodilution (tg-6-HD) to a physiologic hematocrit (e.g., 0.44) tg-6-HD mice returned the CBF to wt levels. Cerebral blood flow was determined in another transgenic mouse line that overexpresses human Epo in the brain only (tg-21): CBF increased by 17% compared with wt controls. However, oxygen delivery was similar in all four mouse groups tested (wt, tg-6, tg-6-HD and tg-21). Mean CMR(glc) was higher in tg-6 (+72%), tg-6-HD mice (+43%) and tg-21 (+22%) than in wt mice. Local CMR(glc) was higher in all 40 brain regions in tg-6 but only in 15 and 8 regions in tg-6-HD and tg-21 mice. These results show that prolonged increases in hematocrit did not alter cerebral oxygen delivery at a decreased CBF and increased CMR(glc). Hemodilution suggests that high blood viscosity is a cause of the decrease in CBF and partly of the increase in CMR(glc). Cerebral glucose metabolic rate may also be increased by a direct effect of Epo in the brain (tg-21 mice).

Animals↗
PubMed2006

The heterogeneity of human mesenchymal stem cell preparations--evidence from simultaneous analysis of proteomes and transcriptomes.

OBJECTIVE: Mesenchymal stem cells (MSC) raise high hopes in clinical applications. However, the lack of common standards and a precise definition of MSC preparations remains a major obstacle in research and application of MSC. Whereas surface antigen markers have failed to precisely define this population, a combination of proteomic data and microarray data provides a new dimension for the definition of MSC preparations. METHODS: In our continuing effort to characterize MSC, we have analyzed the differential transcriptome and proteome expression profiles of MSC preparations isolated from human bone marrow under two different expansion media (BM-MSC-M1 and BM-MSC-M2). RESULTS: In proteomics, 136 protein spots were unambiguously identified by MALDI-TOF-MS and corresponding cDNA spots were selected on our "Human Transcriptome cDNA Microarray." Combination of datasets revealed a correlation in differential gene expression and protein expression of BM-MSC-M1 vs BM-MSC-M2. Genes involved in metabolism were more highly expressed in BM-MSC-M1, whereas genes involved in development, morphogenesis, extracellular matrix, and differentiation were more highly expressed in BM-MSC-M2. Interchanging culture conditions for 8 days revealed that differential expression was retained in several genes whereas it was altered in others. CONCLUSION: Our results have provided evidence that homogeneous BM-MSC preparations can reproducibly be isolated under standardized conditions, whereas culture conditions exert a prominent impact on transcriptome, proteome, and cellular organization of BM-MSC.

Cell Culture Techniques↗
PubMed2006

Changes in the serum proteome of patients with sepsis and septic shock.

BACKGROUND: Sepsis is still the leading cause of death in the intensive care unit. Our goal was to elucidate potential early differences in serum between survivors (SURV) and non-survivors (NON-SURV) on day 28. METHODS: We applied proteomic technology to serum samples of patients with sepsis and septic shock. Serum samples from 18 patients with sepsis and septic shock were obtained during the first 12 h after diagnosis of septic shock. Patients were grouped into SURV and NON-SURV on day 28. RESULTS: Seven patients survived and 11 patients died. Using proteome analysis, two-dimensional gel electrophoresis detected more than 200 spots per gel. A differential protein expression was discovered between SURV and NON-SURV, whereby protein alterations not yet described in sepsis were revealed. CONCLUSIONS: Our results show that proteomic profiling is a useful approach for detecting protein expression dynamics in septic patients, and may bring us closer to achieving a comprehensive molecular profiling compared with genetic studies alone.

Adult↗
PubMed2005

The hematopoietic factor G-CSF is a neuronal ligand that counteracts programmed cell death and drives neurogenesis.

G-CSF is a potent hematopoietic factor that enhances survival and drives differentiation of myeloid lineage cells, resulting in the generation of neutrophilic granulocytes. Here, we show that G-CSF passes the intact blood-brain barrier and reduces infarct volume in 2 different rat models of acute stroke. G-CSF displays strong anti-apoptotic activity in mature neurons and activates multiple cell survival pathways. Both G-CSF and its receptor are widely expressed by neurons in the CNS, and their expression is induced by ischemia, which suggests an autocrine protective signaling mechanism. Surprisingly, the G-CSF receptor was also expressed by adult neural stem cells, and G-CSF induced neuronal differentiation in vitro. G-CSF markedly improved long-term behavioral outcome after cortical ischemia, while stimulating neural progenitor response in vivo, providing a link to functional recovery. Thus, G-CSF is an endogenous ligand in the CNS that has a dual activity beneficial both in counteracting acute neuronal degeneration and contributing to long-term plasticity after cerebral ischemia. We therefore propose G-CSF as a potential new drug for stroke and neurodegenerative diseases.

Animals↗
PubMed2005

Stem cell proteomes: a profile of human mesenchymal stem cells derived from umbilical cord blood.

Multipotent mesenchymal stem cells (MSCs) derived from human umbilical cord blood (UCB) represent promising candidates for the development of future strategies in cellular therapy. To create a comprehensive protein expression profile for UCB-MSCs, one UCB unit from a full-term delivery was isolated from the unborn placenta, transferred into culture, and their whole-cell protein fraction was subjected to two-dimensional electrophoresis (2-DE). Unambiguous protein identification was achieved with peptide mass fingerprinting matrix-assisted laser desorption/ionization - time of flight - mass spectrometry (MALDI-TOF-MS), peptide sequencing (MALDI LIFT-TOF/TOF MS), as well as gel-matching with previously identified databases. In overall five replicate 2-DE runs, a total of 2037 +/- 437 protein spots were detected of which 205 were identified representing 145 different proteins and 60 isoforms or post-translational modifications. The identified proteins could be grouped into several functional categories, such as metabolism, folding, cytoskeleton, transcription, signal transduction, protein degradation, detoxification, vesicle/protein transport, cell cycle regulation, apoptosis, and calcium homeostasis. The acquired proteome map of nondifferentiated UCB-MSCs is a useful inventory which facilitates the identification of the normal proteomic pattern as well as its changes due to activated or suppressed pathways of cytosolic signal transduction which occur during proliferation, differentiation, or other experimental conditions.

Databases, Protein↗
PubMed2004

Tumor necrosis factor-like weak inducer of apoptosis-induced neurodegeneration.

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of the tumor necrosis factor (TNF) family of cytokines. It has proangiogenic and proinflammatory properties in vivo and induces cell death in tumor cell lines. TWEAK effects are mediated by the membrane receptor Fn14. In a systematic search for genes regulated in a murine stroke model with the tag-sequencing technique massively parallel signature sequencing, we have identified TWEAK as an induced gene. After 24 hr of focal cerebral ischemia in vivo or oxygen glucose deprivation in primary cortical neurons, both TWEAK and its receptor Fn14 were significantly upregulated. TWEAK induced cell death in primary neurons. Transfection of a nuclear factor (NF)-kappaB-luciferase fusion gene demonstrated that TWEAK stimulated transcriptional activity of NF-kappaB through Fn14 and the IkappaB kinase. Inhibition of NF-kappaB reduced TWEAK-stimulated neuronal cell death, suggesting that NF-kappaB mediates TWEAK-induced neurodegeneration at least in part. Intraperitoneal injection of a neutralizing anti-TWEAK antibody significantly reduced the infarct size after 48 hr of permanent cerebral ischemia. In summary, our data show that TWEAK induces neuronal cell death and is involved in neurodegeneration in vivo.

Animals↗
PubMed2004

Correlation between local monocarboxylate transporter 1 (MCT1) and glucose transporter 1 (GLUT1) densities in the adult rat brain.

Monocarboxylate transporters type 1 (MCT1) facilitate the transport of monocarboxylates across cell membranes of the blood-brain barrier and brain parenchymal cells. The present study had two aims: (1) to determine the local distribution of MCT1 in the brain; and (2) to compare the local densities of MCT1 with the local densities of the main nutritional transporters, glucose transporter GLUT1. Using immunoautoradiography of cryosections from rat brain, 32 brain structures were analyzed. (1) A heterogenous distribution pattern of MCT1 densities was observed throughout the brain. Compared to brain homogenate (100%), MCT1 densities ranged from 43 to 164% in the brain structures investigated. Local GLUT1 densities showed a comparable range (35-145%). (2) A close correlation was found between local MCT1 and local GLUT1 densities. As local GLUT1 densities reflect local glucose metabolism in the brain, we conclude that local MCT1 densities are adjusted to local glucose metabolism and transport.

Animals↗
PubMed2004

The path to enlightenment: making sense of genomic and proteomic information.

Whereas genomics describes the study of genome, mainly represented by its gene expression on the DNA or RNA level, the term proteomics denotes the study of the proteome, which is the protein complement encoded by the genome. In recent years, the number of proteomic experiments increased tremendously. While all fields of proteomics have made major technological advances, the biggest step was seen in bioinformatics. Biological information management relies on sequence and structure databases and powerful software tools to translate experimental results into meaningful biological hypotheses and answers. In this resource article, I provide a collection of databases and software available on the Internet that are useful to interpret genomic and proteomic data. The article is a toolbox for researchers who have genomic or proteomic datasets and need to put their findings into a biological context.

Computational Biology↗
PubMed2004

Comprehensive proteome expression profiling of undifferentiated versus differentiated neural stem cells from adult rat hippocampus.

Adult neural stem cells can be isolated from various regions of the rat brain and seem to have multilineage differentiation potential. In this study, we investigated the hypothesis that global protein expression of adult neural stem cells isolated from rat hippocampus is changed during in vitro differentiation. After 2 days of differentiation, we separated total protein extracts by two-dimensional gel electrophoresis and used mass spectrometry and gel-matching for identification. We detected a differential expression in 367 regulated protein spots, of which 128 could be identified. Regulated proteins included participants in transcription and DNA metabolism; signal transduction and Ca2+-signaling; MAP kinase pathways; cytoskeletal rearrangement; regulation of cell cycle, proliferation, and survival; protein biosynthesis, folding, and degradation; and glycine and glutamate metabolic pathways. These results suggest a massive reorganization of the stem cell proteomic profile upon differentiation and indicate potential cellular targets mediating the differentiation of neural stem cells.

Animals↗
PubMed2004

Alterations in rat brain proteins after desflurane anesthesia.

BACKGROUND: Volatile anesthetics disappear from an organism after the end of anesthesia. Whether changes of protein expression persist in the brain for a longer period is not known. This study investigates the question of whether the expression of proteins is altered in the rat brain after the end of desflurane anesthesia. METHODS: Three groups (n = 12 each) of rats were anesthetized with 5.7% desflurane in air for 3 h. Brains were removed directly after anesthesia, 24 h after anesthesia, or 72 h after anesthesia. Two additional groups (n = 12 each) served as naive conscious controls, in which the brains were removed without previous anesthesia 3 or 72 h after the start of the experiment. Cytosolic proteins were isolated. A proteome-wide study was performed, based on two-dimensional gel electrophoresis and mass spectrometry. RESULTS: Compared with conscious controls, significant (P < 0.05) increase/decrease was found: 3 h of anesthesia, 5/2 proteins; 24 h after anesthesia, 13/1 proteins; 72 h after anesthesia, 6/4 proteins. The overall changes in protein expression as quantified by the induction factor ranged from -1.67 (decrease to 60%) to 1.79 (increase by 79%) compared with the controls (100%). Some of these regulated proteins play a role in vesicle transport and metabolism. CONCLUSION: Desflurane anesthesia produces changes in cytosolic protein expression up to 72 h after anesthesia in the rat brain, indicating yet unknown persisting effects.

Anesthesia, Inhalation↗
PubMed2004

Cloning of a novel neuronally expressed orphan G-protein-coupled receptor which is up-regulated by erythropoietin, interacts with microtubule-associated protein 1b and colocalizes with the 5-hydroxytryptamine 2a receptor.

G-protein-coupled receptors (GPCRs) are the largest group of cell surface molecules involved in signal transduction and are receptors for a wide variety of stimuli ranging from light, calcium and odourants to biogenic amines and peptides. It is assumed that systematic genomic data-mining has identified the overwhelming majority of all remaining GPCRs in the genome. Here we report the cloning of a novel orphan GPCR which was identified in a search for erythropoietin-induced genes in the brain as a strongly up-regulated gene. This unknown gene coded for a protein which had a seven-transmembrane topology and key features typical of GPCRs of the A family but a low overall identity to all known GPCRs. The protein, coded ee3, has an unusually high evolutionary conservation and is expressed in neurons in diverse areas of the CNS with relation to integrative functions or motor tasks. A yeast two-hybrid screen for interacting proteins revealed binding to the microtubule-associated protein (MAP) 1b. Coupling to MAP1a has been described for another cognate GPCR, the 5-hydroxytryptamine (5HT) 2a receptor. Surprisingly, we found complete colocalization of ee3 and the 5HT2a receptor. The interaction with MAP1b proved to be critical for the stability or folding of ee3 as in mice lacking MAP1b the ee3 protein was undetectable by immunohistochemistry, although messenger RNA levels remained unchanged. We propose that ee3 is a highly interesting new orphan GPCR with potential connections to erythropoietin and 5HT2a receptor signalling.

Amino Acid Sequence↗
PubMed2003

The proteome of human brain microdialysate.

BACKGROUND: Cerebral microdialysis has been established as a monitoring tool in neurocritically ill patients suffering from severe stroke. The technique allows to sample small molecules in the brain tissue for subsequent biochemical analysis. In this study, we investigated the proteomic profile of human cerebral microdialysate and if the identified proteins might be useful predictors for disease characteristics in stroke for tissue at risk in the contralateral hemisphere. We analysed cerebral protein expression in microdialysate from three stroke patients sampled from the hemisphere contralateral to the lesion. Using a proteomic approach based on two-dimensional gel electrophoresis and subsequent mass spectrometry, we created a protein map for the global protein expression pattern of human microdialyste. RESULTS: We found an average of 158 +/- 24 (N = 18) protein spots in the human cerebral microdialysate and could identify 95 spots, representing 27 individual proteins. Most of these have been detected in human cerebrospinal fluid before, but 10 additional proteins mainly of cerebral intracellular origin were identified exclusively in the microdialysate. CONCLUSIONS: The 10 proteins found exclusively in human cerebral microdialysate, but not in cerebrospinal fluid, indicate the possibility to monitor the progression of the disease towards deterioration. The correlation of protein composition in the human cerebral microdialysate with the patients' clinical condition and results of cerebral imaging may be a useful approach to future applications for neurological stroke diagnosis, prognosis, and treatment.

Journal Article↗
PubMed2003

Expression of vascular endothelial growth factor and its receptors in rat neural stem cells.

Neural stem cells serve neurogenesis in several areas of the adult mammalian brain. The present study investigates an additional feature, i.e. the expression of vascular endothelial growth factor (VEGF) and its receptors in cultured neurospheres from hippocampus, subventricular zone, and olfactory bulb in adult rats. RT-PCR showed that all three lines expressed VEGF mRNA, but different sets of VEGF receptor mRNAs. Stimulation by either 50 ng/ml VEGF-A165 or by 24 h of anoxia resulted in an altered pattern of receptor expression for VEGF-R2 (Flk-1), VEGF-R3 (Flt-4), neuropilin-1, and neuropilin-2, whereas VEGF-R1 (Flt-1) remained unexpressed. The basal expression of VEGF and of several of its receptor mRNAs indicates a hitherto unknown angiogenic potential of neural stem cells.

Animals↗
PubMed2003

The proteome of neural stem cells from adult rat hippocampus.

BACKGROUND: Hippocampal neural stem cells (HNSC) play an important role in cerebral plasticity in the adult brain and may contribute to tissue repair in neurological disease. To describe their biological potential with regard to plasticity, proliferation, or differentiation, it is important to know the cellular composition of their proteins, subsumed by the term proteome. RESULTS: Here, we present for the first time a proteomic database for HNSC isolated from the brains of adult rats and cultured for 10 weeks. Cytosolic proteins were extracted and subjected to two-dimensional gel electrophoresis followed by protein identification through mass spectrometry, database search, and gel matching. We could map about 1141 PlusMinus; 209 (N = 5) protein spots for each gel, of which 266 could be identified. We could group the identified proteins into several functional categories including metabolism, protein folding, energy metabolism and cellular respiration, as well as cytoskeleton, Ca2+ signaling pathways, cell cycle regulation, proteasome and protein degradation. We also found proteins belonging to detoxification, neurotransmitter metabolism, intracellular signaling pathways, and regulation of DNA transcription and RNA processing. CONCLUSIONS: The HNSC proteome database is a useful inventory which will allow to specify changes in the cellular protein expression pattern due to specific activated or suppressed pathways during differentiation or proliferation of neural stem cells. Several proteins could be identified in the HNSC proteome which are related to differentiation and plasticity, indicating activated functional pathways. Moreover, we found a protein for which no expression has been described in brain cells before.

Journal Article↗
PubMed2002

Cerebral transcriptome analysis of transgenic mice overexpressing erythropoietin.

Erythropoietin (EPO) and its receptor are expressed in the brain, and one of its roles appears to be neuroprotection. This study investigates whether chronic overexpression of EPO changes brain mRNA expression in the brains of transgenic mice. Therefore, cerebral mRNA expression was investigated in transgenic mice overexpressing EPO. Microarray analysis revealed an upregulation (2.8- to 3.6-fold) of N-acetylglucosamine-6-O-sulfotransferase (prolongation of the EPO effect), a translocase of the inner mitochondrial membrane (mitochondrial matrix import of nuclear encoded proteins), a mitochondrial ribosomal protein (mitochondrial protein translation), and a peroxisomal biogenesis factor (formation of peroxisomes). In conclusion, components of oxidative metabolism pathways were activated at the level of transcription which could be related to neuroprotective effects of EPO or could indicate compromised tissue.

Animals↗
PubMedDate not supplied

Comparison of statistical approaches for the analysis of proteome expression data of differentiating neural stem cells.

Comparative proteomic studies often use statistical tests included in the software for the analysis of digitized images of two-dimensional electrophoresis gels. As these programs include only limited capabilities for statistical analysis, many studies do not further describe their statistical approach. To find potential differences produced by different data processing, we compared the results of (1) Student's t-test using a spreadsheet program, (2) the intrinsic algorithms implemented in the Phoretix 2D gel analysis software, and (3) the SAM algorithm originally developed for microarray analysis. We applied the algorithms to proteome data of undifferentiated neural stem cells versus in vitro differentiated neural stem cells. We found (1) 367 spots differentially expressed using Student's t-test, (2) 203 spots using the algorithms in Phoretix 2D, and (3) 119 spots using the algorithms in SAM, respectively, with an overlap of 42 spots detected by all three algorithms. Applying different statistical approaches on the same dataset resulted in divergent set of protein spots labeled as statistically "significant". Currently, there is no agreement on statistical data processing of 2DE datasets, but the statistical tests applied in 2DE studies should be documented. Tools for the statistical analysis of proteome data should be implemented and documented in the existing 2DE software.

Animals↗