ISSN:0892-6638    

DOI:10.1096/fasebj.7.2.8440405

出版商:Wiley    

年代:1993

数据来源: WILEY

摘要:

This is a report on Symposia organized by the International Society for Bioelectricity and presented at the 1992 FASEB Meeting. The presentations summarized here were intended to provide a sampling of new and fruitful lines of research. The theme topics for the Symposia were cancer, neural function, cell signaling, pineal gland function, and immune system interactions. Living organisms are complex electrochemical systems that evolved over billions of years in a world with a relatively simple weak magnetic field and with few electromagnetic energy emitters. As is characteristic of living organisms, they interacted with and adapted to this environment of electric and magnetic fields. In recent years there has been a massive introduction of equipment that emits electromagnetic fields in an enormous range of new frequencies, modulations, and intensities. As living organisms have only recently found themselves immersed in this new and virtually ubiquitous environment, they have not had the opportunity to adapt to it. This gives us, as biologists, the opportunity to use these electromagnetic fields as probes to study the functioning of living systems. This is a significant opportunity, as new approaches to studying living systems so often provide the means to make great leaps in science. In recent years, a diversity of biologists have carried out experiments using electromagnetic fields to study the function of living cells and systems. This approach is now becoming quite fruitful and is yielding data that are advancing our knowledge in diverse areas of biology.— Frey, A. H. Electromagnetic field interactions with biological systems.FASEB J.7: 272‐281; 1993.

ISSN:0892-6638    

DOI:10.1096/fasebj.7.2.8440406

出版商:Wiley    

年代:1993

数据来源: WILEY

摘要:

Aminoacyl tRNA synthetases are divided into two unrelated classes of ten enzymes each. Members from each class specifically aminoacylate small RNA oligonucleotides lacking anticodon sequences. Duplex structures with only four base pairs stabilized by RNA tetraloop motifs are active. Atomic groups on bases and ribose 2′‐hydroxyl groups in the RNA minor groove make functional contacts that are essential for aminoacylation and provide the high specificity. A system for specific aminoacylation of small RNA oligonucleotides that is based on sequences proximal to the amino acid attachment site may reflect the small sizes of early synthetases.— Musier‐Forsyth, K., Schimmel, P. Aminoacylation of RNA oligonucleotides: minimalist structures and origin of specificity.FASEB J.7: 282‐289; 1993.

ISSN:0892-6638    

DOI:10.1096/fasebj.7.2.7680012

出版商:Wiley    

年代:1993

数据来源: WILEY

摘要:

Aminopeptidases catalyze the cleavage of amino acids from the amino terminus of protein or peptide substrates. They are widely distributed throughout the animal and plant kingdoms and are found in many subcellular organelles, in cytoplasm, and as membrane components. Several aminopeptidases perform essential cellular functions. Many, but not all, of these peptidases are zinc metalloenzymes and are inhibited by the transition‐state analog bestatin. Some are monomeric, and others are assemblies of relatively high mass (50 kDa) subunits. cDNA sequences are available for several aminopeptidases, and a 3‐dimensional structure is available for the bovine lens enzyme. Crystallographic, electron micrographic, NMR, and photoaffinity labeling studies indicate that lens leucine aminopeptidase protomers are bilobal and that bestatin and substrates are bound in an active site, which is found in the larger lobe on each protomer. Zn2+is involved in substrate liganding in most aminopeptidases. There is no evidence of an acyl‐enzyme intermediate in hydrolysis. Amino acid sequences determined directly or deduced from cDNAs indicate some amino acid sequence homologies in organisms as diverse asEscherichia coliand mammals, particularly in catalytically important residues or in residues involved in metal ion binding.— Taylor, A. Aminopeptidases: structure and function.FASEB J.7: 290‐298; 1993.

ISSN:0892-6638    

DOI:10.1096/fasebj.7.2.8440407

出版商:Wiley    

年代:1993

数据来源: WILEY

摘要:

Corticotropin‐releasing factor (CRF), the key neuropeptide in the stress cascade, has major inhibitory actions on testicular function in addition to its known antireproductive effects at the central level (inhibition of sexual behavior and LH secretion). CRF is secreted by the Leydig cells of the testis and acts through high‐affinity receptors at the Leydig cell membrane as a potent negative regulator of LH action, inhibiting gonadotropin‐induced cAMP generation and androgen production. CRF is also a primary stimulus ofβ‐endorphin secretion by the Leydig cells, which in turn exerts paracrine inhibition of FSH action in the tubular compartment of the testis through high‐affinity receptors in the Sertoli cells. CRF action in the Leydig cells involves a pertussis toxin‐insensitive guanyl nucleotide regulatory unit. In contrast to CRF receptors in the brain, pituitary, and other peripheral tissues, those in the Leydig cell are not coupled to Gs. The inhibitory action of CRF in the Leydig cell is exerted through protein kinase C, at the level of the catalytic subunit of adenylate cyclase. The secretion of CRF by the Leydig cell is stimulated by LH, acting via release of serotonin (5HT) and autocrine activation of 5HT2receptors. Serotonin acts on 5HT2receptors in the Leydig cell to stimulate CRF secretion via a pertussis toxin insensitive G‐protein and presumably through activation of phosphoinositide hydrolysis. The diversity of the biochemical responses to CRF and 5HT2receptor activation (i.e., inhibition of adenylate cyclase at the cytoplasmic aspect of the cell membrane vs. stimulation of CRF release from secretion granules) may reflect the stimulation of different protein kinase C isoenzymes. The LH å 5HT å CRF inhibitory loop serves to continuously buffer the stimulation of androgen production by gonadotropin. 5HT, the immediate stimulus of testicular CRF secretion, is released during stress and is locally increased in the testis in pathological conditions associated with impaired testicular function (i.e., orchitis, varicocele). Also, propranolol, theβ‐adrenergic antagonist frequently used in the control of blood pressure in patients with hypertension and often associated with impotence, acts via a serotonergic mechanism to stimulate CRF secretion and causes marked inhibition of LH‐induced cAMP production and steroidogenesis in cultured Leydig cells. These basic studies of 5HT and CRF are relevant to the pathogenesis of testicular dysfunction and for the development of antagonist therapies to block CRF production and its local antireproductive effects.— Dufau, M. L., Tinajero, J. C., Fabbri, A. Corticotropin releasing factor: an antireproductive hormone of the testis.FASEB J.7: 299‐307; 1993.

ISSN:0892-6638    

DOI:10.1096/fasebj.7.2.8382638

出版商:Wiley    

年代:1993

数据来源: WILEY

摘要:

von Willebrand factor is a multimeric glycoprotein essential for the normal arrest of bleeding after tissue injury (hemostasis). The molecule is present in blood, both in plasma and inside platelets, as well as in endothelial cells and the subendothelial matrix of the vessel wall. Through multiple functional domains, von Willebrand factor mediates the attachment of platelets to exposed tissues, where discontinuity of the vascular endothelium occurs, and the subsequent platelet aggregation leading to the formation of platelet thrombi. The crucial role of von Willebrand factor in platelet function is particularly apparent when hemodynamic conditions create blood flow with high shear stress, as in capillaries under physiologic conditions or in stenosed and partially occluded arteries in disease states. The involvement of von Willebrand factor in the processes that lead to acute thrombosis has attracted considerable interest on the molecular and functional biology of the protein. Indeed, understanding the mechanisms and structural bases for von Willebrand factor function may result in new and effective approaches to anti‐thrombotic intervention.— Ruggeri, Z. M., and Ware, J. von Willebrand factor.FASEB J.7: 308‐316; 1993.

ISSN:0892-6638    

DOI:10.1096/fasebj.7.2.8440408

出版商:Wiley    

年代:1993

数据来源: WILEY

摘要:

Vitamin A and related molecules — the retinoids — play essential roles in vision, growth, reproduction, and cellular differentiation beginning in early development. Retinoic acid, a key regulatory retinoid formed intracellularly through the oxidation of retinol, functions as ligand for a family of nuclear retinoic acid receptors that regulate transcription from target genes. Metabolic events are critical to maintaining physiological concentrations of retinoic acid. In the cytoplasm, retinol, retinaldehyde, and retinoic acid are associated with retinoid‐binding proteins, most of which are ~ 15‐kDa proteins belonging to the fatty acid‐binding protein/cellular retinol‐binding protein family. The ligand binding properties and molecular features of these proteins have been well characterized. Recent experiments have highlighted the importance of the cellular retinoid‐binding proteins in controlling the concentration of free retinoids and in directing protein‐bound retinoids to key enzymes responsible for their metabolism. For example, the cellular retinol‐binding protein, CRBP, has been implicated in retinol uptake, retinol esterification, mobilization of retinyl esters, and the initial oxidation of retinol to retinaldehyde. The ligands bound to other retinoid‐binding proteins have also been shown to be available for enzymatic transformation. The new knowledge of the various ways these cytoplasmic proteins buffer the concentration of ligand, control their distribution, and determine their metabolism by specific enzymes is contributing to an improved understanding of the physiological control of retinoid action.— Ross, A. C. Cellular metabolism and activation of retinoids: roles of cellular retinoid‐binding proteins.FASEB J.7: 317‐327; 1993.

ISSN:0892-6638    

DOI:10.1096/fasebj.7.2.8440409

出版商:Wiley    

年代:1993

数据来源: WILEY

摘要:

Cyclic GMP is recognized as an important intracellular mediator of extracellular signals such as nitric oxide and natriuretic peptides. Cyclic GMP interacts with three types of intracellular receptor proteins: cGMP‐dependent protein kinases, cGMP‐regulated ion channels, and cGMP‐regulated cyclic nucleotide phosphodiesterases. This means that cGMP can alter cell function through protein phosphorylation or through mechanisms not directly related to protein phosphorylation. Cyclic GMP appears to regulate a number of intracellular processes, such as vascular smooth muscle relaxation and neutrophil activation, through these receptor proteins in the cell. It is also becoming clear that the localization of these cGMP receptor proteins in the cell is an important factor in the regulation of cell function by cGMP.— Lincoln, T. M.; Cornwell, T. L. Intracellular cyclic GMP receptor proteins.FASEB J.7: 328‐338; 1993.

ISSN:0892-6638    

DOI:10.1096/fasebj.7.2.7680013

出版商:Wiley    

年代:1993

数据来源: WILEY

摘要:

With the recent discoveries of novel forms of phospholipases A2(PLA2S),2new schemes for the roles of various PLA2Sin lipid metabolism must be considered. The type II 14‐kDa PLA2isolated from human synovial fluid or platelet has many of the biochemical characteristics of the homologous snake venom and mammalian pancreatic PLA2S, It appears to function both as a cell‐associated enzyme and extracellularly, where its expression and/or release is regulated by a variety of mediators such as cytokines or growth factors. The mammalian 85‐kDa PLA2purified from monocytic cells or platelets has no sequence homology to the 14‐kDa PLA2and exhibits biochemically different characteristics. It translocates from cytosol to particulate cell fractions in the presence of submicromolar levels of Ca2+and has a substrate preference forsn‐2‐arachidonoyl–ontaining phospholipids. The cellular function and relative importance of these two enzymes in lipid metabolism remain to be determined. In this review, the biochemistry, localization, function, and regulation of these two distinct mammalian Ca2+‐de pendent PLA2are compared.—‐Mayer, R. J.; Marshall, L. A. New insights on mammalian phospholipase A2(s); comparison of arachidonoyl‐selective and ‐nonselective enzymes.FASEB J.7: 339‐348; 1993.

ISSN:0892-6638    

DOI:10.1096/fasebj.7.2.8440410

出版商:Wiley    

年代:1993

数据来源: WILEY

摘要:

Nitric oxide (NO) is a small, gaseous, paramagnetic radical with a high affinity for interaction with ferrous hemoproteins such as soluble guanylate cyclase and hemoglobin. Interest in NO measurement increased exponentially with the discovery that NO or a related compound is the endothelium‐derived relaxing factor (EDRF). In addition to being a potent endogenous vasodilator, NO has a role in inflammation, thrombosis, immunity, and neurotransmission. Measurement of NO is important as many of its effects (e.g., vasodilatation, inhibition of platelet aggregation) are similar to those of other substances produced by the endothelium, such as prostacyclin. NO is formed in small amounts in vivo and is rapidly destroyed by interaction with oxygen, making measurement difficult. A computerized search of the past five year's literature found NO measurements reported in fewer than 50 of 955 articles dealing with EDRF. Inhibitors of NO synthesis such as the arginine analogs or agents that inactivate NO, such as reduced hemoglobin, are commonly used as specific probes for NO, in vivo and in vitro; however, none of the NO inhibitors is completely specific. The most widely used assays use one of three strategies to detect NO: 1) NO is “trapped” by nitroso compounds, or reduced hemoglobin, forming a stable adduct that is detected by electron paramagnetic resonance (EPR) (detection threshold ≈ 1 nmol);2) NO oxidizes reduced hemoglobin to methemoglobin, which is detected by spectrophotometry (detection threshold ≈ 1 nmol);3) NO interacts with ozone producing light, “chemiluminescence” (detection threshold ≈ 20 pmol). These assays can be performed to exclusively detect NO, or by adding acid and reducing agents to the sample, can measure NO and related oxides of nitrogen such as nitrite. Several new amperometric microelectrode assays offer the potential to measure smaller amounts of NO (10–20M), permitting NO measurement in intact issues and from single cells. This review describes the pharmacology and toxicology of NO and reviews the major techniques for measuring NO in biological models.— Archer, S. Measurement of nitric oxide in biological models.FASEB J.7: 349‐360; 1993.

ISSN:0892-6638    

DOI:10.1096/fasebj.7.2.8440411

出版商:Wiley    

年代:1993

数据来源: WILEY