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Mammalian Tissues (mammalian + tissue)
Selected AbstractsNeuropharmacology and therapeutic potential of cannabinoidsADDICTION BIOLOGY, Issue 1 2000Roger G. Pertwee Mammalian tissues contain at least two types of cannabinoid receptor, CB 1, found mainly on neurones and CB 2, found mainly in immune cells. Endogenous ligands for these receptors have also been identified. These endocannabinoids and their receptors constitute the endogenous cannabinoid system. Two cannabinoid receptor agonists, ,9 -tetrahydrocannabinol and nabilone, are used clinically as anti-emetics or to boost appetite. Additional therapeutic uses of cannabinoids may include the suppression of some multiple sclerosis and spinal injury symptoms, the management of pain, bronchial asthma and glaucoma, and the prevention of neurotoxicity. There are also potential clinical applications for CB 1 receptor antagonists, in the management of acute schizophrenia and cognitive/memory dysfunctions and as appetite suppressants. Future research is likely to be directed at characterizing the endogenous cannabinoid system more completely, at obtaining more conclusive clinical data about cannabinoids with regard to both beneficial and adverse effects, at developing improved cannabinoid formulations and modes of administration for use in the clinic and at devising clinical strategies for separating out the sought-after effects of CB 1 receptor agonists from their psychotropic and other unwanted effects. [source] The cannabinoid CB2 receptor: a good friend in the gutNEUROGASTROENTEROLOGY & MOTILITY, Issue 9 2007A. A. Izzo Abstract, Mammalian tissues express the cannabinoid 1 (CB1) receptor and the cannabinoid 2 (CB2) receptor, the latter being involved in inflammation and pain. In somatic nerve pathways, the analgesic effects of CB2 agonism are well documented. Two papers published in the Journal have provided evidence that CB2 receptor activation inhibits visceral afferent nerve activity in rodents. These exciting findings are discussed in the context of recent data highlighting the emerging role of CB2 receptor as a critical target able to counteract hypermotility in pathophysiological states, gut inflammation and possibly colon cancer. [source] SSAO/VAP-1 protein expression during mouse embryonic developmentDEVELOPMENTAL DYNAMICS, Issue 9 2008Tony Valente Abstract SSAO/VAP-1 is a multifunctional enzyme depending on in which tissue it is expressed. SSAO/VAP-1 is present in almost all adult mammalian tissues, especially in highly vascularised ones and in adipocytes. SSAO/VAP-1 is an amine oxidase able to metabolise various endogenous or exogenous primary amines. Its catalytic activity can lead to cellular oxidative stress, which has been implicated in several pathologies (atherosclerosis, diabetes, and Alzheimer's disease). The aim of this work is to achieve a study of SSAO/VAP-1 protein expression during mouse embryogenesis. Our results show that SSAO/VAP-1 appears early in the development of the vascular system, adipose tissue, and smooth muscle cells. Moreover, its expression is strong in several epithelia of the sensory organs, as well as in the development of cartilage sites. Altogether, this suggests that SSAO/VAP-1 enzyme could be involved in the differentiation processes that take place during embryonic development, concretely in tissue vascularisation. Developmental Dynamics 237:2585,2593, 2008. © 2008 Wiley-Liss, Inc. [source] REVIEW FOR SPECIAL ISSUE ON CANNABINOIDS: Ligands that target cannabinoid receptors in the brain: from THC to anandamide and beyondADDICTION BIOLOGY, Issue 2 2008Roger G. Pertwee ABSTRACT A major finding,that (,)- trans -,9 -tetrahydrocannabinol (,9 -THC) is largely responsible for the psychotropic effects of cannabis,prompted research in the 1970s and 1980s that led to the discovery that this plant cannabinoid acts through at least two types of cannabinoid receptor, CB1 and CB2, and that ,9 -THC and other compounds that target either or both of these receptors as agonists or antagonists have important therapeutic applications. It also led to the discovery that mammalian tissues can themselves synthesize and release agonists for cannabinoid receptors, the first of these to be discovered being arachidonoylethanolamide (anandamide) and 2-arachidonoylglycerol. These ,endocannabinoids' are released onto their receptors in a manner that appears to maintain homeostasis within the central nervous system and sometimes either to oppose or to mediate or exacerbate the unwanted effects of certain disorders. This review provides an overview of the pharmacology of cannabinoid receptors and their ligands. It also describes actual and potential clinical uses both for cannabinoid receptor agonists and antagonists and for compounds that affect the activation of cannabinoid receptors less directly, for example by inhibiting the enzymatic hydrolysis of endocannabinoids following their release. [source] The human skin/chick chorioallantoic membrane model accurately predicts the potency of cosmetic allergensEXPERIMENTAL DERMATOLOGY, Issue 4 2009Dan Slodownik Abstract:, The current standard method for predicting contact allergenicity is the murine local lymph node assay (LLNA). Public objection to the use of animals in testing of cosmetics makes the development of a system that does not use sentient animals highly desirable. The chorioallantoic membrane (CAM) of the chick egg has been extensively used for the growth of normal and transformed mammalian tissues. The CAM is not innervated, and embryos are sacrificed before the development of pain perception. The aim of this study was to determine whether the sensitization phase of contact dermatitis to known cosmetic allergens can be quantified using CAM-engrafted human skin and how these results compare with published EC3 data obtained with the LLNA. We studied six common molecules used in allergen testing and quantified migration of epidermal Langerhans cells (LC) as a measure of their allergic potency. All agents with known allergic potential induced statistically significant migration of LC. The data obtained correlated well with published data for these allergens generated using the LLNA test. The human-skin CAM model therefore has great potential as an inexpensive, non-radioactive, in vivo alternative to the LLNA, which does not require the use of sentient animals. In addition, this system has the advantage of testing the allergic response of human, rather than animal skin. [source] Tolerance to low O2: lessons from invertebrate genetic modelsEXPERIMENTAL PHYSIOLOGY, Issue 2 2006Gabriel G. Haddad There have been extensive studies and experiments on cells, tissues and animals that are susceptible to low O2, and many pathways have been discovered that can lead to injury in mammalian tissues. But other pathways that can help in the survival of low O2 have also been discovered in these same tissues. It should be noted, however, that the mechanisms that can lead to better survival in susceptible mammalian tissues have quantitatively a ,narrow range' for recovery, since these tissues are inherently at risk. Another strategy for understanding the susceptibility of organisms is to learn about pathways used by anoxia-resistant animals. Approximately a decade ago, I and my co-workers discovered that one such animal, Drosophila melanogaster, is very tolerant of low O2. Here, I detail some of the studies that we performed and the strategies that we developed to understand the mechanisms that underlie the fascinating resistance of Drosophila to measured partial pressure of O2 of zero. We employed three ideas to try to address our questions: (1) mutagenesis screens to identify loss-of-function mutants; (2) microarrays on adapted versus naïve flies; and (3) studying cell biology and physiology of genes that seem important in flies and mammals. The hope is to learn from these studies about the fundamental basis of tolerance to the lack of O2, and with this knowledge be able to develop better therapies for the future. [source] Identification of a 250 kDa putative microtubule-associated protein as bovine ferritinFEBS JOURNAL, Issue 3 2005Evidence for a ferritin, microtubule interaction We reported previously on the purification and partial characterization of a putative microtubule-associated protein (MAP) from bovine adrenal cortex with an approximate molecular mass of 250 kDa. The protein was expressed ubiquitously in mammalian tissues, and bound to microtubules in vitro and in vivo, but failed to promote tubulin polymerization into microtubules. In the present study, partial amino acid sequencing revealed that the protein shares an identical primary structure with the widely distributed iron storage protein, ferritin. We also found that the putative MAP and ferritin are indistinguishable from each other by electrophoretic mobility, immunological properties and morphological appearance. Moreover, the putative MAP conserves the iron storage and incorporation properties of ferritin, confirming that the two are structurally and functionally the same protein. This fact led us to investigate the interaction of ferritin with microtubules by direct electron microscopic observations. Ferritin was bound to microtubules either singly or in the form of large intermolecular aggregates. We suggest that the formation of intermolecular aggregates contributes to the intracellular stability of ferritin. The interactions between ferritin and microtubules observed in this study, in conjunction with the previous report that the administration of microtubule depolymerizing drugs increases the serum release of ferritin in rats [Ramm GA, Powell LW & Halliday JW (1996) J Gastroenterol Hepatol11, 1072,1078], support the probable role of microtubules in regulating the intracellular concentration and release of ferritin under different physiological circumstances. [source] Synchronized transcriptional gene expression of H+ -ATP synthase subunits in different tissues of Fischer 344 rats of different agesFEBS JOURNAL, Issue 23 2000Toshiki Himeda Little is known about the relationship between the stoichiometry of polypeptides of multisubunit enzyme complexes and the absolute amount of each transcript of the complexes in mammalian tissues. Here we showed that the absolute amounts of the transcripts of most subunits of rat H+ -ATP synthase examined greatly differed in the different tissues, showing the following hierarchy of tissue-specificity: heart > kidney > brain , liver. However, surprisingly, there was no difference in the expression pattern of these in terms of the molar ratio of each transcript, indicating a nearly similar stoichiometric expression pattern irrespective of tissue or age of the rat. Therefore, the present finding clearly indicates that most of the transcripts of the 16 subunits of rat H+ -ATP synthase were concertedly and synchronously expressed, having a constant expression pattern of the transcripts, irrespective of tissue or age of the rats. This is the first report of the absolute amounts of the transcripts of this multisubunit enzyme. [source] Engineering Nanoassemblies of PolysaccharidesADVANCED MATERIALS, Issue 28 2010Soheil Boddohi Abstract Polysaccharides offer a wealth of biochemical and biomechanical functionality that can be used to develop new biomaterials. In mammalian tissues, polysaccharides often exhibit a hierarchy of structure, which includes assembly at the nanometer length scale. Furthermore, their biochemical function is determined by their nanoscale organization. These biological nanostructures provide the inspiration for developing techniques to tune the assembly of polysaccharides at the nanoscale. These new polysaccharide nanostructures are being used for the stabilization and delivery of drugs, proteins, and genes, the engineering of cells and tissues, and as new platforms on which to study biochemistry. In biological systems polysaccharide nanostructures are assembled via bottom-up processes. Many biologically derived polysaccharides behave as polyelectrolytes, and their polyelectrolyte nature can be used to tune their bottom-up assembly. New techniques designed to tune the structure and composition of polysaccharides at the nanoscale are enabling researchers to study in detail the emergent biological properties that arise from the nanoassembly of these important biological macromolecules. [source] Enzymatic and immunochemical evaluation of phospholipid hydroperoxide glutathione peroxidase (PHGPx) in testes and epididymal spermatozoa of rats of different agesINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 2 2002Federica Tramer Selenium (Se) and selenoproteins such as glutathione peroxidases are necessary for the proper development and fertilizing capacity of sperm cells. Phospholipid hydroperoxide glutathione peroxidase (PHGPx, E.C. 1.11.1.12) is a monomeric seleno-enzyme present in different mammalian tissues in soluble and bound form. Its function, like the other glutathione peroxidases, was originally viewed as a protective role against hydroperoxides, but direct and indirect evidence indicates that it has additional regulatory roles. PHGPx is present in testis cells and sperm cells, and its appearance is hormone regulated. We present here biochemical data, which clearly indicate that the enzyme specific activity in rat is age-dependent during the life-span monitored (from 36 to 365 days), with a maximum at 3 months of age in the testis germ cells and at 6 months of age in the isolated epididymal sperm cells. Western blotting and immunocytochemical analysis by means of anti-PHGPx antibodies show the different distribution and the strong binding of PHGPx in the testes and sperm cell subcellular compartments (nucleus, acrosome, mitochondria and residual bodies) of rats of different age. The presence of the protein exhibits in the testis cells a pattern different from that of the catalytic activity, with a maximum at 6 months of age. The subcellular distribution of PHGPx is qualitatively, but not quantitatively, unchanged during ageing. These different behaviours are compared and discussed. [source] Kinetic Analysis of L -Carnosine Formation by ,-AminopeptidasesADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 2-3 2010Tobias Heck Abstract The ,,,-dipeptide L -carnosine occurs in high concentrations in long-lived innervated mammalian tissues and is widely sold as a food additive. On a large scale L -carnosine is produced by chemical synthesis procedures. We have established two aqueous enzymatic reaction systems for the preparation of L -carnosine using the dissolved bacterial ,-aminopeptidases DmpA from Ochrobactrum anthropi and BapA from Sphingosinicella xenopeptidilytica as catalysts and investigated the kinetics of the enzyme-catalyzed peptide couplings. DmpA catalyzed the formation of L -carnosine from C-terminally activated ,-alanine derivatives (acyl donor) and L -histidine (acyl acceptor) in an aqueous reaction mixture at pH,10 with high catalytic rates (Vmax=19.2,,mol,min,1 per mg of protein, kcat=12.9,s,1), whereas Vmax in the BapA-catalyzed coupling reaction remained below 1.4,,mol,min,1 per mg of protein (kcat=0.87,s,1). Although the equilibrium of this reaction lies on the side of the hydrolysis products, the reaction is under kinetic control and L -carnosine temporarily accumulated to concentrations that correspond to yields of more than 50% with respect to the employed acyl donor. However, competing nucleophiles caused unwanted hydrolysis and coupling reactions that led to decreased product yield and to formation of various peptidic by-products. The substitution of L -histidine for L -histidine methyl ester as acyl acceptor shifted the pKa of the amino functionality from 9.25 to 6.97, which caused a drastic reduction in the amount of coupling by-products in an aqueous reaction system at pH,8. [source] Adult stem cell maintenance and tissue regeneration in the ageing context: the role for A-type lamins as intrinsic modulators of ageing in adult stem cells and their nichesJOURNAL OF ANATOMY, Issue 1 2008Vanja Pekovic Abstract Adult stem cells have been identified in most mammalian tissues of the adult body and are known to support the continuous repair and regeneration of tissues. A generalized decline in tissue regenerative responses associated with age is believed to result from a depletion and/or a loss of function of adult stem cells, which itself may be a driving cause of many age-related disease pathologies. Here we review the striking similarities between tissue phenotypes seen in many degenerative conditions associated with old age and those reported in age-related nuclear envelope disorders caused by mutations in the LMNA gene. The concept is beginning to emerge that nuclear filament proteins, A-type lamins, may act as signalling receptors in the nucleus required for receiving and/or transducing upstream cytosolic signals in a number of pathways central to adult stem cell maintenance as well as adaptive responses to stress. We propose that during ageing and in diseases caused by lamin A mutations, dysfunction of the A-type lamin stress-resistant signalling network in adult stem cells, their progenitors and/or stem cell niches leads to a loss of protection against growth-related stress. This in turn triggers an inappropriate activation or a complete failure of self-renewal pathways with the consequent initiation of stress-induced senescence. As such, A-type lamins should be regarded as intrinsic modulators of ageing within adult stem cells and their niches that are essential for survival to old age. [source] Neural crest-derived stem cells display a wide variety of characteristicsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2009Narihito Nagoshi Abstract A recent burst of findings has shown that neural crest-derived stem cells (NCSCs) can be found in diverse mammalian tissues. In addition to their identification in tissues that are known to be derived from the neural crest, recent studies have revealed NCSCs in tissues that are not specifically derived from the neural crest, such as bone marrow. NCSCs can express a wide range of characteristics, and which properties are expressed mainly depends on their tissue sources and the ontogenic stage of the animal. The identification of NCSCs in various tissues opens an entirely new avenue of approach to developing autologous cell replacement therapies for use in regenerative medicine. In this review, we discuss the origin, migration, and lineage potential of NCSCs from various mammalian tissue sources. J. Cell. Biochem. 107: 1046,1052, 2009. © 2009 Wiley-Liss, Inc. [source] Understanding immune cell trafficking patterns via in vivo bioluminescence imagingJOURNAL OF CELLULAR BIOCHEMISTRY, Issue S39 2002Stefanie Mandl Abstract Cell migration is a key aspect of the development of the immune system and mediating an immune response. There is extensive and continual redistribution of cells to different anatomic sites throughout the body. These trafficking patterns control immune function, tissue regeneration, and host responses to insult. The ability to monitor the fate and function of cells, therefore, is imperative to both understanding the role of specific cells in disease processes and to devising rational therapeutic strategies. Determining the fate of immune cells and understanding the functional changes associated with migration and proliferation require effective means of obtaining in vivo measurements in the context of intact organ systems. A variety of imaging methods are available to provide structural information, such as X-ray CT and MRI, but only recently new tools have been developed that reveal cellular and molecular changes as they occur within living animals. We have pioneered one of these techniques that is based on the observations that light passes through mammalian tissues, and that luciferases can serve as internal biological sources of light in the living body. This method, called in vivo bioluminescence imaging, is a rapid and noninvasive functional imaging method that employs light-emitting reporters and external photon detection to follow biological processes in living animals in real time. This imaging strategy enables the studies of trafficking patterns for a variety of cell types in live animal models of human biology and disease. Using this approach we have elucidated the spatiotemporal trafficking patterns of lymphocytes within the body. In models of autoimmune disease we have used the migration of "pathogenic" immune cells to diseased tissues as a means to locally deliver and express therapeutic proteins. Similarly, we have determined the tempo of NK-T cell migration to neoplastic lesions and measured their life span in vivo. Using bioluminescence imaging individual groups of animals can be followed over time significantly reducing the number of animals per experiment, and improving the statistical significance of a study since changes in a given population can be studied over time. Such rapid assays that reveal cell fates in vivo will increase our basic understanding of the molecular signals that control these migratory pathways and will substantially speed up the development and evaluation of therapies. J. Cell. Biochem. Suppl. 39: 239,248, 2002. © 2002 Wiley-Liss, Inc. [source] Cyclophilin D links programmed cell death and organismal aging in Podospora anserinaAGING CELL, Issue 5 2010Diana Brust Summary Cyclophilin D (CYPD) is a mitochondrial peptidyl prolyl- cis,trans -isomerase involved in opening of the mitochondrial permeability transition pore (mPTP). CYPD abundance increases during aging in mammalian tissues and in the aging model organism Podospora anserina. Here, we show that treatment of the P. anserina wild-type with low concentrations of the cyclophilin inhibitor cyclosporin A (CSA) extends lifespan. Transgenic strains overexpressing PaCypD are characterized by reduced stress tolerance, suffer from pronounced mitochondrial dysfunction and are characterized by accelerated aging and induction of cell death. Treatment with CSA leads to correction of mitochondrial function and lifespan to that of the wild-type. In contrast, PaCypD deletion strains are not affected by CSA within the investigated concentration range and show increased resistance against inducers of oxidative stress and cell death. Our data provide a mechanistic link between programmed cell death (PCD) and organismal aging and bear implications for the potential use of CSA to intervene into biologic aging. [source] Expression of p16INK4a in peripheral blood T-cells is a biomarker of human agingAGING CELL, Issue 4 2009Yan Liu Summary Expression of the p16INK4a tumor suppressor sharply increases with age in most mammalian tissues, and contributes to an age-induced functional decline of certain self-renewing compartments. These observations have suggested that p16INK4a expression could be a biomarker of mammalian aging. To translate this notion to human use, we determined p16INK4a expression in cellular fractions of human whole blood, and found highest expression in peripheral blood T-lymphocytes (PBTL). We then measured INK4/ARF transcript expression in PBTL from two independent cohorts of healthy humans (170 donors total), and analyzed their relationship with donor characteristics. Expression of p16INK4a, but not other INK4/ARF transcripts, appeared to exponentially increase with donor chronologic age. Importantly, p16INK4a expression did not independently correlate with gender or body-mass index, but was significantly associated with tobacco use and physical inactivity. In addition, p16INK4a expression was associated with plasma interleukin-6 concentration, a marker of human frailty. These data suggest that p16INK4a expression in PBTL is an easily measured, peripheral blood biomarker of molecular age. [source] Regulation of Expression of Mammalian Gonadotrophin-Releasing Hormone Receptor GenesJOURNAL OF NEUROENDOCRINOLOGY, Issue 10 2005J. P. Hapgood Abstract Gonadotrophin-releasing hormone (GnRH), acting via its cognate GnRH receptor (GnRHR), is the primary regulator of mammalian reproductive function, and hence GnRH analogues are extensively used in the treatment of hormone-dependent diseases, as well as for assisted reproductive techniques. In addition to its established endocrine role in gonadotrophin regulation in the pituitary, evidence is rapidly accumulating to support the expression and functional roles for two forms of GnRHR (GnRHR I and GnRHR II) in multiple and diverse extra-pituitary mammalian tissues and cells. These findings, together with findings indicating that mutations of the GnRHR are linked to the disease hypogonadotrophic hypogonadism and that GnRHRs play a direct role in neuronal migration and reproductive cancers, have presented new therapeutic targets and intensified research into the structure, function and mechanisms of regulation of expression of GnRHR genes. The present review focuses on the current knowledge on tissue-specific and hormonal regulation of transcription of mammalian GnRH receptor genes. Emerging insights, such as the discovery of diverse regulatory mechanisms in pituitary and extra-pituitary cell types, nonclassical mechanisms of steroid regulation, the use of composite elements for cell-specific expression, the increasing profile of hormones involved in regulation, the complexity of kinase pathways that target the GnRHR I gene, as well as species-differences, are highlighted. Although further research is necessary to understand the mechanisms of regulation of expression of GnRHR I and GnRHR II genes, the GnRHR is emerging as a potential target gene for facilitating cross-talk between neuroendocrine, immune and stress-response systems in multiple tissues via autocrine, paracrine and endocrine signalling. [source] The Pallidin (Pldn) Gene and the Role of SNARE Proteins in Melanosome BiogenesisPIGMENT CELL & MELANOMA RESEARCH, Issue 2 2002Juan M. Falcón-Pérez This review focuses on the product of the pallidin (Pldn) gene, one of a number of genes that in mice are associated with pigmentation defects and platelet dense granule deficiency. A similar combination of defects is also observed in patients suffering from Hermansky,Pudlak (HPS) and Chediak,Higashi (CHS) syndromes. Pldn encodes a novel, ,20-kDa protein that is expressed ubiquitously in mammalian tissues. The pallidin protein was found to bind to syntaxin 13, a member of the syntaxin family of soluble N -ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). As SNARE proteins mediate fusion of intracellular membranes, pallidin may play a role in membrane fusion events required for melanosome biogenesis. [source] Isatin-binding proteins of rat and mouse brain: Proteomic identification and optical biosensor validationPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 1 2010Olga Buneeva Abstract Isatin (indole-2,3-dione) is an endogenous indole that has a distinct and discontinuous distribution in the brain and in other mammalian tissues and body fluids. Its output is increased under conditions of stress and anxiety. Isatin itself and its analogues exhibit a wide range of pharmacological activities but its specific biological targets still are not well characterized. Affinity chromatography of Triton X-100 lysates of soluble and particulate fractions of mouse and rat whole brain homogenates on 5-aminocaproyl-isatin-Sepharose followed by subsequent proteomic analysis resulted in identification of 65 and 64 individual proteins, respectively. Isatin-binding capacity of some of the identified proteins has been validated in an optical biosensor study using a Biacore 3000 optical biosensor, 5-aminocarproyl-isatin, and 5-aminoisatin as the affinity ligands. The Kd values (of 0.1,20,,M) obtained during the optical biosensor experiments were consistent with the range of Kd values recently reported for [3H]isatin binding to brain sections. Although the number of isatin-binding proteins identified in the mouse and rat brain was similar, only 21 proteins (about one-third) were identical in the two species. This may be one reason for the differences in isatin effects in rats and mice reported in the literature. [source] Crystallization and preliminary X-ray crystallographic studies of recombinant human betaine,homocysteine S-methyltransferaseACTA CRYSTALLOGRAPHICA SECTION D, Issue 3 2001Nandita Bose Betaine,homocysteine S-methyltransferase (BHMT) catalyzes a reaction essential for regulation of methionine and homocysteine metabolism and the catabolism of choline in mammalian tissues. Human recombinant BHMT (MW = 45,kDa) has been crystallized by the hanging-drop vapor-diffusion method at 294,K using ethylene glycol as the precipitant. The crystals belong to the monoclinic space group C2, with unit-cell parameters a = 109.190, b = 91.319, c = 88.661,Å, , = 122.044°, and diffract to 2.9,Å resolution on a local rotating-anode X-ray source. Rotation-function analysis and the Matthews coefficient, VM = 2.46,Å3,Da,1, are consistent with a dimer in the asymmetric unit, suggesting that the active enzyme is a tetramer with 222 symmetry. [source] Mitochondrial biogenesis: Which part of "NO" do we understand?BIOESSAYS, Issue 6 2003Scot C. Leary A recent paper by Nisoli et al.1 provides the first evidence that elevated levels of nitric oxide (NO) stimulate mitochondrial biogenesis in a number of cell lines via a soluble guanylate-cyclase-dependent signaling pathway that activates PGC1, (peroxisome proliferator-activated receptor , coactivator-1,), a master regulator of mitochondrial content. These results raise intriguing possibilities for a role of NO in modulating mitochondrial content in response to physiological stimuli such as exercise or cold exposure. However, whether this signaling cascade represents a widespread mechanism by which mammalian tissues regulate mitochondrial content, and how it might integrate with other pathways that control PGC1, expression, remain unclear. BioEssays 25:538,541, 2003. © 2003 Wiley Periodicals, Inc. [source] Physiological roles of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligandBIOFACTORS, Issue 1 2009Takayuki Sugiura Abstract 2-Arachidonoylglycerol is an arachidonic acid-containing monoacylglycerol isolated from the rat brain and canine gut as an endogenous ligand for the cannabinoid receptors (CB1 and CB2). 2-Arachidonoylglycerol binds to both the CB1 receptor, abundantly expressed in the nervous system, and the CB2 receptor, mainly expressed in the immune system, with high affinity, and exhibits a variety of cannabimimetic activities. Notably, anandamide, another endogenous ligand for the cannabinoid receptors, acts as a partial agonist at these cannabinoid receptors, whereas 2-arachidonoylglycerol acts as a full agonist. The results of structure-activity relationship experiments strongly suggested that 2-arachidonoylglycerol rather than anandamide is the true natural ligand for both the CB1 and the CB2 receptors. Evidence is gradually accumulating which shows that 2-arachidonoylglycerol plays physiologically and pathophysiologically essential roles in various mammalian tissues and cells. © 2009 International Union of Biochemistry and Molecular Biology, Inc. [source] Trace amine-associated receptors and their ligandsBRITISH JOURNAL OF PHARMACOLOGY, Issue 8 2006R Zucchi Classical biogenic amines (adrenaline, noradrenaline, dopamine, serotonin and histamine) interact with specific families of G protein-coupled receptors (GPCRs). The term ,trace amines' is used when referring to p- tyramine, ,-phenylethylamine, tryptamine and octopamine, compounds that are present in mammalian tissues at very low (nanomolar) concentrations. The pharmacological effects of trace amines are usually attributed to their interference with the aminergic pathways, but in 2001 a new gene was identified, that codes for a GPCR responding to p- tyramine and ,-phenylethylamine but not to classical biogenic amines. Several closely related genes were subsequently identified and designated as the trace amine-associated receptors (TAARs). Pharmacological investigations in vitro show that many TAAR subtypes may not respond to p- tyramine, ,-phenylethylamine, tryptamine or octopamine, suggesting the existence of additional endogenous ligands. A novel endogenous thyroid hormone derivative, 3-iodothyronamine, has been found to interact with TAAR1 and possibly other TAAR subtypes. In vivo, micromolar concentrations of 3-iodothyronamine determine functional effects which are opposite to those produced on a longer time scale by thyroid hormones, including reduction in body temperature and decrease in cardiac contractility. Expression of all TAAR subtypes except TAAR1 has been reported in mouse olfactory epithelium, and several volatile amines were shown to interact with specific TAAR subtypes. In addition, there is evidence that TAAR1 is targeted by amphetamines and other psychotropic agents, while genetic linkage studies show a significant association between the TAAR gene family locus and susceptibility to schizophrenia or bipolar affective disorder. British Journal of Pharmacology (2006) 149, 967,978. doi:10.1038/sj.bjp.0706948 [source] 2223: Carbon monoxide as a mediator in the retinaACTA OPHTHALMOLOGICA, Issue 2010C BUCOLO Purpose Carbonic monoxide (CO) is organic gas ubiquitously synthesized in mammalian tissues by enzyme that has constitutive and inducible forms. This gas is produced as metabolic end-product in specific cell life phases, and may acts as atypical neuronal messenger. Evidence has recently accumulated suggesting that CO may be cytoprotective because its bioactions, including inhibition of apoptosis, platelet aggregation, complement activation, and inflammatory cytokine production. CO appears to be important to counteract the cytotoxicity caused by excessive production of reactive oxygen (ROS) and nitrogen (RNS) species. Methods In vitro and in vivo models. Results Induction of heme oxygenase (HO)-1 by hemin has been found to prevent retinal cell death after ischemia provoked by ocular hypertension in rats. The LPS-induced expression of pro-inflammatory cytokines, in rat eye, is also inhibited by CO. Interestingly, drugs active as inhibitors of iNOS block CO-induced increases in cGMP in the retina.Drugs inhibiting NO formation by acting on iNOS activity have been found to potently reduce intraocular pressure. Studies from our lab showed that an increase of CO availability by hemin or carbon monoxide-releasing molecules lower the intraocular pressure, suggesting a suppress action of iNOS-derived NO production. Conclusion A better understanding of CO regulation may lead to new therapeutic options that are safer and more efficacious than currently available treatments for various sight-threatening eye diseases, such as retinal degenerations. [source] Significance of endogenous sulphur-containing gases in the cardiovascular systemCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 7 2010Xin-Bao Wang Summary 1. The sulphur-containing gases hydrogen sulphide and sulphur dioxide can be generated endogenously in mammalian tissues and exert significant biological effects in the cardiovascular system. Hydrogen sulphide is considered to be the third novel gasotransmitter in addition to nitric oxide and carbon monoxide. The present review describes the effects of hydrogen sulphide on the cardiovascular system and its possible mechanisms under physiological conditions. We also discuss the pathophysiological effects of hydrogen sulphide on cardiovascular diseases. The therapeutic potential of hydrogen sulphide is summarized. 2. We recently discovered that sulphur dioxide, another endogenous sulphur-containing gas, has important physiological and pathophysiological roles in the cardiovascular system. To some extent, the effect of sulphur dioxide is similar to that of the other gasotransmitters nitric oxide, carbon monoxide and hydrogen sulphide. Sulphur dioxide may also be a novel gas mediator in the cardiovascular system. [source] | |||||||||||||||||||||||||