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Results for “Functional proteome”

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At least 559 records · Page 31Linked to original sources
PubMed2005

Glycation of mitochondrial proteins from diabetic rat kidney is associated with excess superoxide formation.

Chronic hyperglycemia causes structural alterations of proteins through the Maillard reaction. In diabetes, methylglyoxal (MGO)-induced hydroimidazolones are the predominant modification. In contrast to acute hyperglycemia, mitochondrial respiration is depressed in chronic diabetes. To determine whether MGO-derived protein modifications result in abnormalities in mitochondrial bioenergetics and superoxide formation, proteomics and functional studies were performed in renal cortical mitochondria isolated from rats with 2, 6, and 12 mo of streptozotocin-induced diabetes. MGO-modified proteins belonged to the following two pathways: 1) oxidative phosphorylation and 2) fatty acid beta-oxidation. Two of these proteins were identified as components of respiratory complex III, the major site of superoxide production in health and disease. Mitochondria from rats with diabetes exhibited a diminution of oxidative phosphorylation. A decrease in the respiratory complex III activity was significantly correlated with the quantity of MGO-derived hydroimidazolone present on mitochondrial proteins in both diabetic and control animals. In diabetes, isolated renal mitochondria produced significantly increased quantities of superoxide and showed evidence of oxidative damage. Administration of aminoguanidine improved mitochondrial respiration and complex III activity and decreased oxidative damage to mitochondrial proteins. Therefore, posttranslational modifications of mitochondrial proteins by MGO may represent pathogenic events leading to mitochondria-induced oxidative stress in the kidney in chronic diabetes.

2,4-Dinitrophenol↗
PubMed2000

Research in the exercise sciences: where do we go from here?

The goal of this article is to provide a perspective on how research involving the acute and chronic effects of exercise (referred to as "exercise sciences") on the structure and function of organs systems will evolve in the next century. Within the last 30 years, exercise-related research has rapidly transitioned from an organ to a subcellular/molecular focus. Thus future research will continue to be heavily influenced by molecular biology tools, fueled by both emerging technologies (e.g., "gene-chip microarrays") designed to dissect gene function on a macro scale as well as by the completion of the human genome project in which the approximately 80,000 genes comprising humans will be completely sequenced. These successes will drive the emerging fields of functional genomics (the dissecting of a gene's identity and function) and proteomics (the study of the properties of proteins). Funding levels at the National Institutes of Health will likely increase in order to expand these emerging fields as well as provide avenues for translating fundamental knowledge into solving the complexities of a number of degenerative diseases influenced heavily by activity/inactivity factors such as cardiopulmonary disease, diabetes, obesity, and the debilitating disorders associated with aging. Thus there are many challenges facing future exercise scientists who must harness the new technologies and take an aggressive stance in bringing this important field to the forefront.

Aging↗
PubMed2005

Host-environment interactions: their impact on progression from gastric inflammation to carcinogenesis and on development of new approaches to prevent and treat gastric cancer.

Revelation of the connection between Helicobacter pylori infection and gastric adenocarcinoma has prompted new investigations pertaining to its basic and clinical aspects. H. pylori-induced persistent and uncontrolled gastric inflammation nearly always precedes the development of cancer and is instrumental in initiating a multistep process leading to carcinogenesis. Despite initial optimism about the potential of combination anti-H. pylori therapy to ultimately eradicate gastric adenocarcinoma, recent investigations suggest its use should be targeted and tailored to a selected patient group considering the multifaceted role of H. pylori in disease and the disease heterogeneity of gastric adenocarcinoma. The clinical spectrum of H. pylori infection ranges from asymptomatic gastritis and peptic ulcer to gastric malignancies. The occurrence of one versus another is the result of differences in the magnitude of gastritis, and the current disease paradigm suggests gastric inflammation is common to all H. pylori-associated gastroduodenal diseases. Therefore, the host inflammatory responses to environmental triggers, rather than to bacteria or environmental factors per se, would dictate the variable outcomes of H. pylori infection. Putative factors that are expected to play an important role in stimulating inflammatory pathways and modulating the cross-talk between host and environment are age at the time of infection, environmental cofactors, H. pylori virulence, and host genetics. Elucidation of the intimate relationship between host-environment interaction and gastric inflammation, although currently a formidable task, is essential in the development of new prevention and treatment strategies. Such knowledge might provide clues that allow more accurate prediction of variable outcomes of gastric inflammation and appropriate adjustment of treatment strategies, and might open up novel areas for studying gastric carcinogenesis. The evolving new technologies, such as microarray, proteomic, and functional genomic analyses, promise to shed new light on the immense complexity of the presumed host-environment interactions and will reveal more useful markers for the diagnosis and prognosis of gastric adenocarcinoma.

Adenocarcinoma↗
PubMed2004

GOTree Machine (GOTM): a web-based platform for interpreting sets of interesting genes using Gene Ontology hierarchies.

BACKGROUND: Microarray and other high-throughput technologies are producing large sets of interesting genes that are difficult to analyze directly. Bioinformatics tools are needed to interpret the functional information in the gene sets. RESULTS: We have created a web-based tool for data analysis and data visualization for sets of genes called GOTree Machine (GOTM). This tool was originally intended to analyze sets of co-regulated genes identified from microarray analysis but is adaptable for use with other gene sets from other high-throughput analyses. GOTree Machine generates a GOTree, a tree-like structure to navigate the Gene Ontology Directed Acyclic Graph for input gene sets. This system provides user friendly data navigation and visualization. Statistical analysis helps users to identify the most important Gene Ontology categories for the input gene sets and suggests biological areas that warrant further study. GOTree Machine is available online at http://genereg.ornl.gov/gotm/. CONCLUSION: GOTree Machine has a broad application in functional genomic, proteomic and other high-throughput methods that generate large sets of interesting genes; its primary purpose is to help users sort for interesting patterns in gene sets.

Animals↗
PubMed2004

Biology of primate relaxin: a paracrine signal in early pregnancy?

Relaxin is a peptide hormone that exerts numerous effects in a variety of tissues across a broad range of species. Although first identified more than 75 years ago interest in relaxin biology has waxed and waned over the years consistent with peaks and troughs of new experimental data on its wide-ranging biological effects and advances in relaxin enabling technologies. Recent insights into species-dependent differences in relaxin biology during pregnancy have once again stimulated a relative surge of interest in the study of relaxin's reproductive biology. Identification and pharmacological characterization of orphaned relaxin receptors and exploration of its paracrine effects on pregnancy using genomic and proteomic technologies have succeeded in fueling current interest in relaxin research. Primates and non-primate vertebrates exhibit very disparate profiles of relaxin genomics, proteomics and functional biology. Non-human primates appear to exhibit a very close similarity to humans with respect to relaxin reproductive biology but the similarities and subtle differences are only just beginning to be understood. We, and others, have shown that relaxin produces significant changes to the non-human primate endometrium during the peri-implantation period that are consistent with relaxin's long perceived role as a paracrine modulator of pregnancy. The purpose of this review is to summarize the reproductive biology of relaxin in non-human primates with a specific emphasis on the paracrine role of ovarian and endometrial relaxin during embryo implantation and early pregnancy.

Animals↗
PubMed2006

Post-genomics of the model haloarchaeon Halobacterium sp. NRC-1.

Halobacteriumsp. NRC-1 is an extremely halophilic archaeon that is easily cultured and genetically tractable. Since its genome sequence was completed in 2000, a combination of genetic, transcriptomic, proteomic, and bioinformatic approaches have provided insights into both its extremophilic lifestyle as well as fundamental cellular processes common to all life forms. Here, we review post-genomic research on this archaeon, including investigations of DNA replication and repair systems, phototrophic, anaerobic, and other physiological capabilities, acidity of the proteome for function at high salinity, and role of lateral gene transfer in its evolution.

Journal Article↗
PubMed2003

Study of PTPC composition during apoptosis for identification of viral protein target.

The permeability transition pore complex (PTPC), a mitochondrial polyprotein complex, has been previously described to be involved in the control of mitochondrial membrane permeabilization (MMP) during chemotherapy-induced apoptosis. PTPC may contain proteins from both mitochondrial membranes [e.g., voltage-dependent anion channel (VDAC), PRAX-1, peripheral benzodiazepine receptor (PBR), adenine nucleotide translocator (ANT)], from cytosol (e.g., hexokinase II, glycerol kinase), from matrix [e.g., cyclophilin D (CypD)], and from intermembrane space (e.g., creatine kinase). PTPC may also interact with tumor suppressor proteins (i.e., Bax and Bid), oncoprotein homologues of Bcl-2 and some viral proteins, which can regulate apoptosis induced by pore opening. ANT and VDAC are the target of numerous pro-apoptotic MMP inducers. However, the precise composition of PTPC as well as the respective role of each PTPC component represent major issues in the understanding MMP process. Using several experimental strategies that combine co-immunoprecipitation, proteomics, and functional tests with proteoliposomes, we and others have been able to characterize some of the intra/inter-PTPC protein interactions leading to a better understanding of the process of MMP. In addition, this approach could identify new putative members and regulators of PTPC pro-apoptotic function and new targets of viral protein involved in the modulation of apoptosis during infection.

Animals↗
PubMed2002

Strategies to identify disease genes.

The correlation between genes and disease began in earnest in the early 1900s with the identification of Mendelian-like inheritance of "inborn errors of metabolism." Since then, the ever-broadening field of genetics has been established as one of the most important and groundbreaking branches of science and medicine to date. With the announcement of a "working draft" sequence of the human genome in 2001, the vast array of both genomic and expressed sequence information available in the public databases alone has meant that the concept of hunting for genes is evolving. Nowadays, researchers can substitute many labor-intensive hours in the lab for less time searching on the World Wide Web. Specialization within genetics has been continuously providing subsets of the genre such as genomics, pharmacogenetics, chemogenomics, gene therapy, proteomics and functional genomics, all of which are based on the fundamental starting block, the gene. This review aims to summarize both traditional and current strategies for identifying susceptibility and monogenetic disease genes and describes how these strategies have evolved in tune with the ever-expanding wealth of information now available at our fingertips.

Animals↗
PubMed2004

Will we ever understand? The undescribable diversity of the prokaryotes.

This communication will summarize recent estimations on prokaryotic cell numbers, technical aspects of the exploration of the hidden diversity of the as-yet-uncultured prokaryotes and their function in the environment, recognition of novel major lines of descent, elucidation of novel metabolic pathways and attempts to improve the definition of the taxon species. These are some of recent highlights that will reflect only incompletely recent advances of microbiologist and other aspects of diversity at the genomic level, including the tremendous influence of whole genome sequences on the development of DNA macro- and microarrays for rapid identification of genes and specimen, the annotation of gene sequences to gene function by proteomics and the recognition of the extent of lateral gene transfer in the evolution of the genome, hence of contemporary organisms. As an example of modern trends in systematics three new families will be described for recently described genera, namely Thermoleophilaceae, Solirubrobacteraceae and Conexibacteraceae, which are phylogenetically positioned among environmental clone sequences at the root of the class Actinobacteria.

Bacteria↗
PubMed2006

Major advances in fundamental dairy cattle nutrition.

Fundamental nutrition seeks to describe the complex biochemical reactions involved in assimilation and processing of nutrients by various tissues and organs, and to quantify nutrient movement (flux) through those processes. Over the last 25 yr, considerable progress has been made in increasing our understanding of metabolism in dairy cattle. Major advances have been made at all levels of biological organization, including the whole animal, organ systems, tissues, cells, and molecules. At the whole-animal level, progress has been made in delineating metabolism during late pregnancy and the transition to lactation, as well as in whole-body use of energy-yielding substrates and amino acids for growth in young calves. An explosion of research using multicatheterization techniques has led to better quantitative descriptions of nutrient use by tissues of the portal-drained viscera (digestive tract, pancreas, and associated adipose tissues) and liver. Isolated tissue preparations have provided important information on the interrelationships among glucose, fatty acid, and amino acid metabolism in liver, adipose tissue, and mammary gland, as well as the regulation of these pathways during different physiological states. Finally, the last 25 yr has witnessed the birth of "molecular biology" approaches to understanding fundamental nutrition. Although measurements of mRNA abundance for proteins of interest already have provided new insights into regulation of metabolism, the next 25 yr will likely see remarkable advances as these techniques continue to be applied to problems of dairy cattle biology. Integration of the "omics" technologies (functional genomics, proteomics, and metabolomics) with measurements of tissue metabolism obtained by other methods is a particularly exciting prospect for the future. The result should be improved animal health and well being, more efficient dairy production, and better models to predict nutritional requirements and provide rations to meet those requirements.

Absorption↗
PubMed2003

New understanding in cardiotoxicity.

Interest in cardiotoxicity has dramatically increased during the past two years, leading to exciting progress in our understanding of the field. Both clinical and experimental animal studies have emphasized the role of cardiotoxicity in myocardial pathogenesis. Exploration of the cardiotoxicity of air pollution and highly active antiretroviral therapy (HAART) through experimental animal studies have led to mechanistic insights. Novel therapeutic approaches are also under development. Continued efforts to investigate the mechanisms of cardiotoxicity induced by well-known drugs and chemicals, such as Adriamycin, have also generated critical insights into cardiac response to toxicants. Recognition of the significance of cardiotoxicity in myocardial pathogenesis has resulted in the identification of many other drugs or chemicals, such as arsenic trioxide, whose cardiotoxicity is of major concern in clinical applications. Mitochondrial cardiomyopathy, along with control of myocardial cell death, has also become an extensively studied subject. Ionic transport across the inner membrane of mitochondria, especially the function of mitochondrial ATP-sensitive K+ channels and the Ca(2+)-activated K+ channels in myocardial protection against oxidative injury, has attracted a great deal of attention. Novel approaches, such as functional genomics, proteomics and metabonomics, should significantly improve our understanding of cardiotoxicity.

Air Pollution↗
PubMedDate not supplied

Malaria genome project and its impact on the disease.

Malaria remains uncontrolled to-date due to lack of effective parasite and vector control strategies. With the completion of the host, parasite and vector genome projects more suitable and effective disease control measures can be achieved. Here we have reviewed the Plasmodium falciparum genome project and its impact on malaria research in future. The parasite genome project has revealed certain metabolic pathways which can be targeted to develop antimalarial drugs. It has also identified large number of potential antigens for the future potential vaccines. Now the researchers in the malaria field can plan to take up the studies, which can yield more fruitful results within the limited financial resources using bioinformatics, proteomics, structural, functional and comparative genomics, etc.

Animals↗
PubMed2002

Proteolytic enzymes as therapeutic targets - Keystone Symposium. 3-8 February 2002, Keystone, CO, USA.

The Keystone Symposium 'Proteolytic Enzymes as Therapeutic Targets' was attended by approximately 150 scientists. Around two-thirds of the participants consisted of representatives from pharmaceutical companies, but representatives from academic institutes dominated the list of speakers. The meeting attracted scientists from many different fields, including biochemistry, molecular biology, structural biology, pharmacology, chemistry, and bioinformatics. The science ranged from the discovery and characterization of novel proteinases to the development and clinical trials of proteinase inhibitors and was presented as posters or in oral sessions. The discussions following the oral presentations were always very animated, but hardly ever heated. Although there were a few new drugs being presented, the real highlight was the enormous potential of recently discovered proteinases as new therapeutic targets. Both pharmaceutical companies and academic institutes are investing in programs to integrate the avalanche of new information coming from functional genomics, proteomics and structural information to create a platform for applied proteinase technology.

Journal Article↗
PubMed2005

Cytoskeletal networks and pathways involved in endocytosis.

Until recently, the actin cytoskeleton and the endocytic machinery were thought to operate independently. However, the actin cytoskeleton is an integral part of the cell cortex and there is growing evidence in diverse eukaryotes that F-actin plays a direct role during endocytic internalization. Genetic studies in Saccharomyces cerevisiae have demonstrated that Arp2/3-mediated F-actin assembly is required specifically for the internalization step of endocytosis. Using real-time image analysis, we recently defined a pathway for receptor-mediated endocytosis in budding yeast. Many features of this pathway appear to be conserved widely, indicating that principles derived from our studies in yeast will be directly applicable in more complex eukaryotes. We are pursuing our yeast studies using a combined approach involving image analysis, functional genomics, proteomics and biochemistry. These ongoing studies are providing a broader and deeper understanding of the molecular events of endocytosis, of how forces for actin polymerization are harnessed, and of how steps in the pathway are regulated. Our studies in mammalian cells provide evidence that this pathway is conserved in more complex organisms for endocytic and Golgi trafficking events.

Actins↗
PubMed2000

High-throughput protein expression of cDNA products as a tool in functional genomics.

A proteomics approach has been developed aimed to allow high throughput analysis of protein products expressed from cDNA fragments (expressed sequence tags, ESTs). The concept relies on expression of gene products to generate specific antibodies for protein analysis, such as immunolocalization of the proteins on cellular and subcellular level. To evaluate the system, 55 cDNA clones with predominantly unknown function were selected from a mouse testis cDNA-library. A bacterial expression system was designed that allowed robust expression and easy purification. Protein levels between 15 and 80 mg l(-1) were obtained for 49 of the clones. Five clones were selected for immunization and all yielded functional antibodies that gave specific staining in Western blot screening of samples from various cell types. Furthermore, extensive immunolocalization information on subcellular level was obtained for three of the five clones. All generated data were stored in a relational database, and are made available through a web-interface (http://www.biochem.kth.se/multiscale/), which also provides relevant links and allows homology searches from the original sequences. The possibility to allow analysis of gene products from whole genomes using this 'localization proteomics' approach is discussed.

Amino Acid Sequence↗
PubMed2000

Automated protein modelling--the proteome in 3D.

Functional analysis of the proteins discovered in fully sequenced genomes represent the next major challenge of life science research. Computational methods play an increasingly important role in this activity. Among them, comparative protein modelling will play a major role in this challenge, especially in the light of the Structural Genomics programmes about to be started around the world. In recent years, much progress has been made in automating these methods, enabling the production of models for genome scale problems. In this review we discuss how protein models can be applied to functional analysis, as well as some of the current issues and limitations inherent to these methods.

Animals↗
PubMed2006

Toward plasma proteome profiling with ion mobility-mass spectrometry.

Differential, functional, and mapping proteomic analyses of complex biological mixtures suffer from a lack of component resolution. Here we describe the application of ion mobility-mass spectrometry (IMS-MS) to this problem. With this approach, components that are separated by liquid chromatography are dispersed based on differences in their mobilities through a buffer gas prior to being analyzed by MS. The inclusion of the gas-phase dispersion provides more than an order of magnitude enhancement in component resolution at no cost to data acquisition time. Additionally, the mobility separation often removes high-abundance species from spectral regions containing low-abundance species, effectively increasing measurement sensitivity and dynamic range. Finally, collision-induced dissociation of all ions can be recorded in a single experimental sequence while conventional MS methods sequentially select precursors. The approach is demonstrated in a single, rapid (3.3 h) analysis of a plasma digest sample where abundant proteins have not been removed. Protein database searches have yielded 731 high confidence peptide assignments corresponding to 438 unique proteins. Results have been compiled into an initial analytical map to be used -after further augmentation and refinement- for comparative plasma profiling studies.

Blood Proteins↗