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Results for “Biologic pathways”

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At least 847 records · Page 47Linked to original sources
PubMed2004

The perlecan heparan sulfate proteoglycan mediates cellular uptake of HIV-1 Tat through a pathway responsible for biological activity.

Cell surface heparan sulfate proteoglycans (HSPGs) mediate internalization of HIV-1 Tat. Herein, we report that human WiDr cells, which express perlecan but no other HSPGs, can internalize 125I-labeled Tat with minimal lysosomal degradation. Pre-treatment of cells with heparitinase almost completely abolished 125I-Tat surface binding, while the use of an HIV-1 long terminal repeat (LTR) promoter-reporter construct demonstrated that transactivation was potently blocked by pretreatment of cells with heparitinase, indicating an essential role for perlecan in the biologic effects of Tat. We conclude that the perlecan mediates Tat uptake and is required for HIV-1 LTR-directed transactivation in this human cell type.

Cell Line↗
PubMed1998

Acute promyelocytic leukemia as a model for cross-talk between interferon and retinoic acid pathways: from molecular biology to clinical applications.

Acute promyelocytic leukemia (APL) has been regarded as the paradigm for therapeutic approaches utilizing differentiating agents, due to the fact that almost 95% of patients undergo complete remission when treated with all-trans retinoic acid (ATRA). However, complete clinical remission with ATRA alone is always transient, and relapse in APL is almost invariably associated with the acquisition of resistance to ATRA. Acquired resistance to ATRA in APL cell lines and in some APL clinical cases can be partially overcome by interferons (IFNs), cytokines which have well established tumor-growth suppressive activities. APL is associated in 99% of cases with a 15;17 translocation that fuses the PML and Retinoic Acid Receptor alpha (RARalpha) genes. RARalpha is one of the Retinoic Acid (RA) nuclear receptors which mediates, at the transcriptional level, ATRA differentiating and growth suppressive activity. PML is a tumor-growth suppressor whose expression is directly regulated by IFNs. Here we review the molecular mechanisms by which IFNs and RA can cooperate in controlling cell growth and differentiation of normal hemopoietic cells and leukemic cells, focusing on APL as a model system.

Drug Synergism↗
PubMed2005

In silico identification of the key components and steps in IFN-gamma induced JAK-STAT signaling pathway.

Systems biology efforts are increasingly adopting quantitative, mechanistic modeling to study cellular signal transduction pathways and other networks. However, it is uncertain whether the particular set of kinetic parameter values of the model closely approximates the corresponding biological system. We propose that the parameters be assigned statistical distributions that reflect the degree of uncertainty for a comprehensive simulation analysis. From this analysis, we globally identify the key components and steps in signal transduction networks at a systems level. We investigated a recent mathematical model of interferon gamma induced Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathway by applying multi-parametric sensitivity analysis that is based on simultaneous variation of the parameter values. We find that suppressor of cytokine signaling-1, nuclear phosphatases, cytoplasmic STAT1, and the corresponding reaction steps are sensitive perturbation points of this pathway.

Computational Biology↗
PubMed1992

The Entner-Doudoroff pathway: history, physiology and molecular biology.

The Entner-Doudoroff pathway is now known to be very widely distributed in nature. Biochemical and physiological studies show that the Entner-Doudoroff pathway can operate in a linear and catabolic mode, in a 'cyclic' mode, in a modified mode involving non-phosphorylated intermediates, or in alternative modes involving C1 metabolism and anabolism. Molecular and genetic analyses of the Entner-Doudoroff pathway in Zymomonas mobilis, Escherichia coli and Pseudomonas aeruginosa have led to an improved understanding of some fundamental aspects of metabolic controls. It can be argued that the Entner-Doudoroff pathway is more primitive than Embden-Meyerhof-Parnas glycolysis.

Amino Acid Sequence↗
PubMed1992

[Biological role of metabolic pathways from L-arginine to nitric oxide].

This paper reviews recent developments in the biochemistry, pharmacology and physiology of the L-arginine/nitric oxide pathway. Nitric oxide accounts for the biological activity of endothelium-derived relaxing factor (EDRF) and its continuous release plays a crucial role in the regulation of vascular tone and platelet activity. In the nervous system nitric oxide is a neurotransmitter. In the peripheral nervous system, nitroxergic nerves form a part of the non-adrenergic, non-cholinergic innervation of the visceral organs. In the immune system, nitric oxide generated by activated macrophages has tumoricidal and antimicrobial activities. Growing evidence suggests that the alterations in the formation of NO in various tissues contribute to the pathogenesis of various diseases, including hypertension, atherosclerosis, diabetes, subarachnoid hemorrhage and septic shock. Therefore, the improvements in our understanding of the regulation of L-arginine/nitric oxide pathway on the molecular level may lead to the development of new drugs.

Animals↗
PubMed2006

Computational approaches for predicting protein-protein interactions: a survey.

Discovery of the protein interactions that take place within a cell can provide a starting point for understanding biological regulatory pathways. Global interaction patterns among proteins, for example, can suggest new drug targets and aid the design of new drugs by providing a clearer picture of the biological pathways in the neighborhoods of the drug targets. High-throughput experimental screens have been developed to detect protein-protein interactions, however, they show high rates of errors in terms of false positives and false negatives. Many computational approaches have been proposed to tackle the problem of protein-protein interaction prediction. They range from comparative genomics based methods to data integration based approaches. Challenging properties of protein-protein interaction data have to be addressed appropriately before a higher quality interaction map with better coverage can be achieved. This paper presents a survey of major works in computational prediction of protein-protein interactions, explaining their assumptions, main ideas, and limitations.

Humans↗
PubMed2006

Create and assess protein networks through molecular characteristics of individual proteins.

MOTIVATION: The study of biological systems, pathways and processes relies increasingly on analyses of networks. Most often, such analyses focus on network topology, thereby treating all proteins or genes as identical, featureless nodes. Integrating molecular data and insights about the qualities of individual proteins into the analysis may enhance our ability to decipher biological pathways and processes. RESULTS: Here, we introduce a novel platform for data integration that generates networks on the macro system-level, analyzes the molecular characteristics of each protein on the micro level, and then combines the two levels by using the molecular characteristics to assess networks. It also annotates the function and subcellular localization of each protein and displays the process on an image of a cell, rendering each protein in its respective cellular compartment. By thus visualizing the network in a cellular context we are able to analyze pathways and processes in a novel way. As an example, we use the system to analyze proteins implicated with Alzheimers disease and show how the integrated view corroborates previous observations and how it helps in the formulation of new hypotheses regarding the molecular underpinnings of the disease. AVAILABILITY: http://www.rostlab.org/services/pinat.

Cell Physiological Phenomena↗
PubMed1997

DNA structure-dependent checkpoints in model systems.

DNA structure dependent checkpoints require a number of proteins which function to arrest the cell cycle in response to DNA damage (such as UV induced lesions) or blocks to DNA replication. Analogous to a signal transduction pathway, checkpoints communicate information between a DNA lesion and the cell cycle machinery. This brief review will focus on yeast model systems which have been instrumental in identifying the various components (initiating signal, detection, signal transduction and cell cycle effector) of the checkpoint pathways. The biological significance of these pathways in mammalian cells is illustrated in patients with ataxia telangiectasia (AT), a multi-system cancer-prone disorder in which DNA damage checkpoints affecting both DNA replication and mitosis are lost. ATM, the gene mutated in this disorder is structurally related to the yeast rad3/MEC1 checkpoint genes. This demonstrates the high degree of evolutionary conservation of checkpoints amongst eukaryotic organisms.

Adenosine Triphosphatases↗
PubMed2000

Developmental evolutionary biology of the vertebrate ear: conserving mechanoelectric transduction and developmental pathways in diverging morphologies.

This brief overview shows that a start has been made to molecularly dissect vertebrate ear development and its evolutionary conservation to the development of the insect hearing organ. However, neither the patterning process of the ear nor the patterning process of insect sensory organs is sufficiently known at the moment to provide more than a first glimpse. Moreover, hardly anything is known about otocyst development of the cephalopod molluscs, another triploblast lineage that evolved complex 'ears'. We hope that the apparent conserved functional and cellular components present in the ciliated sensory neurons/hair cells will also be found in the genes required for vertebrate ear and insect sensory organ morphogenesis (Fig. 3). Likewise, we expect that homologous pre-patterning genes will soon be identified for the non-sensory cell development, which is more than a blocking of neuronal development through the Delta/Notch signaling system. Generation of the apparently unique ear could thus represent a multiplication of non-sensory cells by asymmetric and symmetric divisions as well as modification of existing patterning process by implementing novel developmental modules. In the final analysis, the vertebrate ear may come about by increasing the level of gene interactions in an already existing and highly conserved interactive cascade of bHLH genes. Since this was apparently achieved in all three lineages of triploblasts independently (Fig. 3), we now need to understand how much of the morphogenetic cascades are equally conserved across phyla to generate complex ears. The existing mutations in humans and mice may be able to point the direction of future research to understand the development of specific cell types and morphologies in the formation of complex arthropod, cephalopod, and vertebrate 'ears'.

Animals↗
PubMed2004

The importance of redox regulated pathways in sperm cell biology.

Redox regulated events are fundamental to our understanding of many cellular pathways and pathological processes. On the one hand, production of reactive oxygen species by mammalian spermatozoa has been associated with a loss of cell function and DNA integrity as a consequence of oxidative stress. These cells are exquisitely sensitive to such damage as a consequence of their relative lack of cytosolic antioxidant enzymes and relative abundance of polyunsaturated fatty acids. Given this susceptibility, it is surprising to discover that spermatozoa are intensely redox active cells and professional generators of reactive oxygen species. The latter are physiologically important to the spermatozoa in regulating every aspect of sperm function examined, including their movement characteristics, capacitation, sperm-zona interaction, the acrosome reaction and sperm-oocyte fusion. The molecular basis of this redox drive is still poorly understood in terms of the source of the reactive oxygen species and the mechanisms by which these reactive metabolites enhance sperm function. Recent advances include the discovery of NOX5 in the male germ line and elucidation of the role of reactive oxygen species in controlling a unique signal transduction cascade associated with sperm capacitation. Given the central importance of redox chemistry in the control of sperm function further research in this area may uncover valuable targets for contraceptive intervention.

Animals↗
PubMed1998

Anti-HIV pronucleotides: decomposition pathways and correlation with biological activities.

The purpose of the present study was to compare the decomposition pathways in CEM cell extracts of various phenyl phosphoramidate derivatives of AZT. In addition, the structures of their metabolites were identified. Correlations with their anti-HIV activities in a thymidine kinase deficient (TK-) CEM cell line have been established with a rationale of designing phosphoramidate pronucleotides capable of delivering intracellularly their respective 5'-nucleoside monophosphate derivatives.

Anti-HIV Agents↗