RESUMEN
Here, we reported the diagnosis and treatment of a case of HIV infected person complicated by an extremely rare infection with Mycobacterium celatum. Due to the similarity of homologous sequence regions between Mycobacterium celatum and Mycobacterium tuberculosis complex, the identification of conventional Mycobacterium species was incorrect, which was corrected after first-generation 16S rRNA sequencing. This report aimed to improve the clinical understanding of Mycobacterium celatum infection and the level of differential diagnosis between non-tuberculous mycobacterial disease and tuberculosis.
Asunto(s)
Infecciones por VIH , Infecciones por Mycobacterium , Mycobacterium , Humanos , ARN Ribosómico 16S/genética , Mycobacterium/genética , Infecciones por Mycobacterium/diagnóstico , Infecciones por Mycobacterium/microbiología , Micobacterias no Tuberculosas/genética , Infecciones por VIH/complicacionesRESUMEN
Extracellular vesicles (EVs) are minute particles secreted by the cells of living organisms, which can encapsulate various bioactive molecules for long-distance transport to present biological functions. With the recent studies on parasite-host interactions, EVs, as a carrier for long-distance transport of worm-derived molecules, have been paid much attention during the across-species regulation of hosts. During schistosome infections, adult worms and eggs have been found to mediate hosts via secretion of EVs. This review presents the advances in the studies on schistosome-host interactions mediated by EVs.
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Vesículas Extracelulares , Schistosoma japonicum , Animales , Transporte Biológico , Interacciones Huésped-Parásitos/fisiología , Schistosoma japonicum/fisiologíaRESUMEN
Yellow catfish (Pelteobagrus fulvidraco) is an important commercial species with high aquaculture potential in China. To better understand the process of digestive functioning of gastric gland development during the larval from 1 dph (day post-hatching) to 30 dph, real-time PCR was used to detect and quantify the pepsinogen and H(+) /K(+) -ATPase gene expression in P. fulvidraco. These data were also compared with the adult situation. The results showed that the expression of pepsinogen and H(+) /K(+) -ATPase genes in P. fulvidraco larvae both started at 1 dph, though the expression level was very low until 3 dph. The quantification of pepsinogen gene expression increased significantly from 4 to 8 dph, increased fluctuantly from 8 to 23 dph and rose sharply from 23 to 30 dph. In comparison with adult fish, there were no significant differences with larvae at 5 and 23 dph. However, data of 10 and 30 dph larvae were obviously higher than those of adult group. H(+) /K(+) -ATPase gene expression increased linearly from 1 to 30 dph. However, it was significantly lower than that of adult. The results show that P. fulvidraco larvae have an earlier functional stomach, though the function of the stomach is still not perfect. There is a gradual acidification environment within the stomach during the P. fulvidraco larvae development. Based on these results, we suggest that the weaning time for P. fulvidraco larvae would be much better after 23 dph.
Asunto(s)
Bagres/anatomía & histología , Bagres/crecimiento & desarrollo , Regulación del Desarrollo de la Expresión Génica/fisiología , ATPasa Intercambiadora de Hidrógeno-Potásio/metabolismo , Pepsinógeno A/metabolismo , Envejecimiento , Animales , Secuencia de Bases , Bagres/clasificación , Regulación Enzimológica de la Expresión Génica , ATPasa Intercambiadora de Hidrógeno-Potásio/genética , Pepsinógeno A/genéticaRESUMEN
Signal peptide-CUB-EGF-like domain-containing protein 3 (SCUBE3) is a secreted glycoprotein that is overexpressed in lung cancer tumor tissues and is correlated with the invasive ability in a lung cancer cell line model. These observations suggest that SCUBE3 may have a role in lung cancer progression. By exogenous SCUBE3 treatment or knockdown of SCUBE3 expression, we found that SCUBE3 could promote lung cancer cell mobility and invasiveness. Knockdown of SCUBE3 expression also suppressed tumorigenesis and cancer metastasis in vivo. The secreted SCUBE3 proteins were cleaved by gelatinases (matrix metalloprotease-2 (MMP-2) and MMP-9) in media to release two major fragments: the N-terminal epidermal growth factor-like repeats and the C-terminal complement proteins C1r/C1s, Uegf and Bmp1 (CUB) domain. Both the purified SCUBE3 protein and the C-terminal CUB domain fragment, bound to transforming growth factor-ß (TGF-ß) type II receptor through the C-terminal CUB domain, activated TGF-ß signaling and triggered the epithelial-mesenchymal transition (EMT). This process includes the induction of Smad2/3 phosphorylation, the increase of Smad2/3 transcriptional activity and the upregulation of the expression of target genes involved in EMT and cancer progression (such as TGF-ß1, MMP-2, MMP-9, plasminogen activator inhibitor type-1, vascular endothelial growth factor, Snail and Slug), thus promoting cancer cell mobility and invasion. In conclusion, in lung cancer cells, SCUBE3 could serve as an endogenous autocrine and paracrine ligand of TGF-ß type II receptor, which could regulate TGF-ß receptor signaling and modulate EMT and cancer progression.
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Proteínas de Unión al Calcio/metabolismo , Transición Epitelial-Mesenquimal , Neoplasias Pulmonares/patología , Factor de Crecimiento Transformador beta/metabolismo , Proteínas de Unión al Calcio/genética , Progresión de la Enfermedad , Técnicas de Silenciamiento del Gen , Humanos , Ligandos , Invasividad Neoplásica , Metástasis de la Neoplasia , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de SeñalRESUMEN
We report on the growth of high-aspect-ratio (approximately > 300) zinc sulfide nanotubes with variable, precisely tunable, wall thicknesses and tube diameters into highly ordered pores of anodic alumina templates by atomic layer deposition (ALD) at temperatures as low as 75 degrees C. Various characterization techniques are employed to gain information on the composition, morphology and crystal structure of the synthesized samples. Besides practical applications, the ALD-grown tubes could be envisaged as model systems for the study of a certain class of size-dependent quantum and classical phenomena.
RESUMEN
A novel receptor guanylyl cyclase (GC) has been identified from the oriental fruit fly Bactrocera dorsalis (Hendel) and has been designated BdmGC-1. Protein domain analysis revealed that BdmGC-1 possesses a characteristic domain organization similar to all known receptor GCs but with a unique carboxyl-terminal extension. When overexpressed in 293T cells, BdmGC-1 manifests as a cell-surface glycoprotein with a marked cGMP-generating activity but is unresponsive to all ligands known to activate mammalian receptor GCs. BdmGC-1 mRNAs were highly expressed during development but had low or no expression in adult tissues. On the basis of its unique sequence and distinct developmental expression pattern, BdmGC-1 represents a novel receptor GC that may play a critical role during the development of B. dorsalis.
Asunto(s)
Regulación del Desarrollo de la Expresión Génica , Receptores Acoplados a la Guanilato-Ciclasa/genética , Tephritidae/genética , Secuencia de Aminoácidos , Animales , Línea Celular , Glicosilación , Humanos , Estadios del Ciclo de Vida , Glicoproteínas de Membrana/análisis , Datos de Secuencia Molecular , Octoxinol , ARN Mensajero , Receptores Acoplados a la Guanilato-Ciclasa/metabolismo , Análisis de Secuencia de ADN , Tephritidae/crecimiento & desarrolloAsunto(s)
Carbofurano/toxicidad , Carcinógenos/efectos adversos , Ciclodextrinas/efectos adversos , Insecticidas/toxicidad , Metil Paratión/toxicidad , Pentaclorofenol/toxicidad , beta-Ciclodextrinas , Animales , Carcinógenos/química , Ciclodextrinas/química , Interacciones Farmacológicas , Larva , Ranidae , SolubilidadRESUMEN
Platelets have a crucial role in the maintenance of normal haemostasis, and perturbations of this system can lead to pathological thrombus formation and vascular occlusion, resulting in stroke, myocardial infarction and unstable angina. ADP released from damaged vessels and red blood cells induces platelet aggregation through activation of the integrin GPIIb-IIIa and subsequent binding of fibrinogen. ADP is also secreted from platelets on activation, providing positive feedback that potentiates the actions of many platelet activators. ADP mediates platelet aggregation through its action on two G-protein-coupled receptor subtypes. The P2Y1 receptor couples to Gq and mobilizes intracellular calcium ions to mediate platelet shape change and aggregation. The second ADP receptor required for aggregation (variously called P2Y(ADP), P2Y(AC), P2Ycyc or P2T(AC)) is coupled to the inhibition of adenylyl cyclase through Gi. The molecular identity of the Gi-linked receptor is still elusive, even though it is the target of efficacious antithrombotic agents, such as ticlopidine and clopidogrel and AR-C66096 (ref. 9). Here we describe the cloning of this receptor, designated P2Y12, and provide evidence that a patient with a bleeding disorder has a defect in this gene. Cloning of the P2Y12 receptor should facilitate the development of better antiplatelet agents to treat cardiovascular diseases.
Asunto(s)
Adenosina Difosfato/metabolismo , Plaquetas/metabolismo , Fibrinolíticos/metabolismo , Proteínas de la Membrana , Canales de Potasio de Rectificación Interna , Receptores Purinérgicos P2/fisiología , Secuencia de Aminoácidos , Animales , Encéfalo/metabolismo , Células CHO , Cromosomas Humanos Par 3 , Clonación Molecular , Cricetinae , AMP Cíclico/metabolismo , ADN Complementario , Femenino , Mutación del Sistema de Lectura , Canales de Potasio Rectificados Internamente Asociados a la Proteína G , Proteínas de Unión al GTP/metabolismo , Hemorragia/metabolismo , Humanos , Masculino , Datos de Secuencia Molecular , Oocitos , Agregación Plaquetaria/fisiología , Potasio/metabolismo , Canales de Potasio/metabolismo , Ratas , Receptores Purinérgicos P2/genética , Receptores Purinérgicos P2/metabolismo , Receptores Purinérgicos P2Y12 , Distribución Tisular , XenopusRESUMEN
The innate immune system uses Toll family receptors to signal for the presence of microbes and initiate host defense. Bacterial lipoproteins (BLPs), which are expressed by all bacteria, are potent activators of Toll-like receptor-2 (TLR2). Here we show that the adaptor molecule, myeloid differentiation factor 88 (MyD88), mediates both apoptosis and nuclear factor-kappaB (NF-kappaB) activation by BLP-stimulated TLR2. Inhibition of the NF-kappaB pathway downstream of MyD88 potentiates apoptosis, indicating that these two pathways bifurcate at the level of MyD88. TLR2 signals for apoptosis through MyD88 via a pathway involving Fas-associated death domain protein (FADD) and caspase 8. Moreover, MyD88 binds FADD and is sufficient to induce apoptosis. These data indicate that TLR2 is a novel 'death receptor' that engages the apoptotic machinery without a conventional cytoplasmic death domain. Through TLR2, BLP induces the synthesis of the precursor of the pro-inflammatory cytokine interleukin-1beta (IL-1beta). Interestingly, BLP also activates caspase 1 through TLR2, resulting in proteolysis and secretion of mature IL-1beta. These results indicate that caspase activation is an innate immune response to microbial pathogens, culminating in apoptosis and cytokine production.
Asunto(s)
Apoptosis/fisiología , Proteínas de Arabidopsis , Proteínas de Drosophila , Glicoproteínas de Membrana/fisiología , Receptores de Superficie Celular/fisiología , Receptores Inmunológicos , Transducción de Señal/fisiología , Proteínas Adaptadoras Transductoras de Señales , Antígenos de Diferenciación/metabolismo , Antígenos de Diferenciación/fisiología , Caspasa 1/metabolismo , Caspasa 8 , Caspasa 9 , Caspasas/metabolismo , Línea Celular , Activación Enzimática , Ácido Graso Desaturasas/metabolismo , Humanos , Factor 88 de Diferenciación Mieloide , FN-kappa B/metabolismo , Unión Proteica , Receptor Toll-Like 2 , Receptores Toll-LikeRESUMEN
One of two orphan photoreceptor guanylyl cyclases that are highly conserved from fish to mammals, GC-E (or retGC1) was eliminated by gene disruption. Expression of the second retinal cyclase (GC-F) as well as the numbers and morphology of rods remained unchanged in GC-E null mice. However, rods isolated from such mice, despite having a normal dark current, recovered from a light flash markedly faster. Unexpectedly, the a- and b-waves of electroretinograms (ERG) from dark-adapted null mice were suppressed markedly. Cones, initially present in normal numbers in the retina, disappeared by 5 weeks, based on ERG and histology. Thus, the GC-E-deficient mouse defines a model for cone dystrophy, but it also demonstrates that morphologically normal rods display paradoxical behavior in their responses to light.
Asunto(s)
Guanilato Ciclasa/genética , Guanilato Ciclasa/metabolismo , Retina/enzimología , Células Fotorreceptoras Retinianas Conos/fisiología , Células Fotorreceptoras Retinianas Bastones/fisiología , Retinitis Pigmentosa/genética , Adaptación Ocular , Animales , Oscuridad , Electrorretinografía , Exones , Guanilato Ciclasa/deficiencia , Ratones , Ratones Endogámicos , Ratones Noqueados , Mapeo Restrictivo , Células Fotorreceptoras Retinianas Conos/patología , Células Fotorreceptoras Retinianas Bastones/patología , Retinitis Pigmentosa/patología , Retinitis Pigmentosa/fisiopatologíaRESUMEN
Human Toll-like receptor 2 (TLR2) is a signaling receptor that responds to LPS and activates NF-kappaB. Here, we investigate further the events triggered by TLR2 in response to LPS. We show that TLR2 associates with the high-affinity LPS binding protein membrane CD14 to serve as an LPS receptor complex, and that LPS treatment enhances the oligomerization of TLR2. Concomitant with receptor oligomerization, the IL-1R-associated kinase (IRAK) is recruited to the TLR2 complex. Intracellular deletion variants of TLR2 lacking C-terminal 13 or 141 aa fail to recruit IRAK, which is consistent with the inability of these mutants to transmit LPS cellular signaling. Moreover, both deletion mutants could still form complexes with wild-type TLR2 and act in a dominant-negative (DN) fashion to block TLR2-mediated signal transduction. DN constructs of myeloid differentiation protein, IRAK, TNF receptor-associated factor 6, and NF-kappaB-inducing kinase, when coexpressed with TLR2, abrogate TLR2-mediated NF-kappaB activation. These results reveal a conserved signaling pathway for TLR2 and IL-1Rs and suggest a molecular mechanism for the inhibition of TLR2 by DN variants.
Asunto(s)
Proteínas de Drosophila , Lipopolisacáridos/inmunología , Glicoproteínas de Membrana/fisiología , Receptores de Superficie Celular/fisiología , Receptores Inmunológicos , Transducción de Señal/inmunología , Proteínas Adaptadoras Transductoras de Señales , Antígenos de Diferenciación/fisiología , Línea Celular , Humanos , Quinasas Asociadas a Receptores de Interleucina-1 , Leucocitos/enzimología , Leucocitos/inmunología , Leucocitos/metabolismo , Receptores de Lipopolisacáridos/biosíntesis , Glicoproteínas de Membrana/biosíntesis , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Factor 88 de Diferenciación Mieloide , FN-kappa B/biosíntesis , FN-kappa B/metabolismo , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/metabolismo , Proteínas Quinasas/metabolismo , Proteínas Quinasas/fisiología , Proteínas Serina-Treonina Quinasas/fisiología , Proteínas/fisiología , Receptores de Superficie Celular/biosíntesis , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/metabolismo , Receptores de Interleucina-1/metabolismo , Receptores de Interleucina-1/fisiología , Eliminación de Secuencia , Factor 6 Asociado a Receptor de TNF , Receptor Toll-Like 2 , Receptores Toll-Like , Quinasa de Factor Nuclear kappa BRESUMEN
The generation of cell-mediated immunity against many infectious pathogens involves the production of interleukin-12 (IL-12), a key signal of the innate immune system. Yet, for many pathogens, the molecules that induce IL-12 production by macrophages and the mechanisms by which they do so remain undefined. Here it is shown that microbial lipoproteins are potent stimulators of IL-12 production by human macrophages, and that induction is mediated by Toll-like receptors (TLRs). Several lipoproteins stimulated TLR-dependent transcription of inducible nitric oxide synthase and the production of nitric oxide, a powerful microbicidal pathway. Activation of TLRs by microbial lipoproteins may initiate innate defense mechanisms against infectious pathogens.
Asunto(s)
Antígenos Bacterianos/inmunología , Proteínas de Drosophila , Interleucina-12/biosíntesis , Lipoproteínas/inmunología , Macrófagos/inmunología , Glicoproteínas de Membrana/metabolismo , Monocitos/inmunología , Mycobacterium tuberculosis/inmunología , Receptores de Superficie Celular/metabolismo , Animales , Antígenos Bacterianos/química , Antígenos Bacterianos/metabolismo , Línea Celular , Regulación de la Expresión Génica , Humanos , Interleucina-12/genética , Lipopolisacáridos/inmunología , Lipoproteínas/química , Lipoproteínas/metabolismo , Macrófagos/metabolismo , Ratones , Monocitos/metabolismo , FN-kappa B/biosíntesis , Óxido Nítrico Sintasa/genética , Óxido Nítrico Sintasa de Tipo II , Regiones Promotoras Genéticas , Transducción de Señal , Receptores Toll-Like , Transcripción Genética , Transfección , Células Tumorales CultivadasRESUMEN
Apoptosis is implicated in the generation and resolution of inflammation in response to bacterial pathogens. All bacterial pathogens produce lipoproteins (BLPs), which trigger the innate immune response. BLPs were found to induce apoptosis in THP-1 monocytic cells through human Toll-like receptor-2 (hTLR2). BLPs also initiated apoptosis in an epithelial cell line transfected with hTLR2. In addition, BLPs stimulated nuclear factor-kappaB, a transcriptional activator of multiple host defense genes, and activated the respiratory burst through hTLR2. Thus, hTLR2 is a molecular link between microbial products, apoptosis, and host defense mechanisms.
Asunto(s)
Apoptosis , Proteínas Bacterianas/farmacología , Proteínas de Drosophila , Lipoproteínas/farmacología , Glicoproteínas de Membrana/metabolismo , Monocitos/citología , Receptores de Superficie Celular/metabolismo , Anticuerpos Monoclonales , Proteínas Bacterianas/metabolismo , Línea Celular/metabolismo , Cicloheximida/farmacología , Citotoxicidad Inmunológica , Genes Reporteros , Humanos , Receptores de Lipopolisacáridos/análisis , Lipopolisacáridos/inmunología , Lipoproteínas/metabolismo , Glicoproteínas de Membrana/inmunología , Monocitos/inmunología , Monocitos/metabolismo , FN-kappa B/metabolismo , Inhibidores de la Síntesis de la Proteína/farmacología , Especies Reactivas de Oxígeno/metabolismo , Receptores de Superficie Celular/inmunología , Transducción de Señal , Acetato de Tetradecanoilforbol/farmacología , Receptor Toll-Like 2 , Receptores Toll-Like , Transfección , Células Tumorales CultivadasRESUMEN
Vertebrates and invertebrates initiate a series of defence mechanisms following infection by Gram-negative bacteria by sensing the presence of lipopolysaccharide (LPS), a major component of the cell wall of the invading pathogen. In humans, monocytes and macrophages respond to LPS by inducing the expression of cytokines, cell-adhesion proteins, and enzymes involved in the production of small proinflammatory mediators. Under pathophysiological conditions, LPS exposure can lead to an often fatal syndrome known as septic shock. Sensitive responses of myeloid cells to LPS require a plasma protein called LPS-binding protein and the glycosylphosphatidylinositol-anchored membrane protein CD14. However, the mechanism by which the LPS signal is transduced across the plasma membrane remains unknown. Here we show that Toll-like receptor 2 (TLR2) is a signalling receptor that is activated by LPS in a response that depends on LPS-binding protein and is enhanced by CD14. A region in the intracellular domain of TLR2 with homology to a portion of the interleukin (IL)-1 receptor that is implicated in the activation of the IL-1-receptor-associated kinase is required for this response. Our results indicate that TLR2 is a direct mediator of signalling by LPS.
Asunto(s)
Proteínas de Drosophila , Lipopolisacáridos/farmacología , Glicoproteínas de Membrana/metabolismo , Proteínas de la Membrana/metabolismo , Receptores de Superficie Celular/metabolismo , Receptores Inmunológicos , Transducción de Señal , Sitios de Unión , Línea Celular , Clonación Molecular , Escherichia coli , Humanos , Receptores de Lipopolisacáridos/metabolismo , Proteínas Recombinantes/metabolismo , Salmonella , Distribución Tisular , Receptor Toll-Like 2 , Receptores Toll-Like , Células Tumorales CultivadasRESUMEN
The dominant cone-rod dystrophy gene CORD6 has previously been mapped to within an 8 cM interval on chromosome 17p12-p13. The retinal-specific guanylate cyclase gene (RETGC-1), which maps to within this genetic interval and previously was implicated in Leber's congenital amaurosis, was screened for mutations within this family and in a panel of small families and individuals with various cone and cone- rod dystrophy phenotypes. A missense mutation (E837D) was identified in affected members of the CORD6 family, as well as a second missense mutation (R838C) in three other families with dominant cone-rod dystrophy. RETGC-1 is only the fourth gene to be implicated in cone-rod dystrophy and this is the first report of dominant mutations in this gene.
Asunto(s)
Guanilato Ciclasa/genética , Mutación/genética , Atrofias Ópticas Hereditarias/genética , Células Fotorreceptoras Retinianas Conos/patología , Células Fotorreceptoras Retinianas Bastones/patología , Adolescente , Adulto , Secuencia de Aminoácidos , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Atrofias Ópticas Hereditarias/enzimología , Atrofias Ópticas Hereditarias/patología , Linaje , Fenotipo , Células Fotorreceptoras Retinianas Conos/enzimología , Células Fotorreceptoras Retinianas Bastones/enzimologíaRESUMEN
We recently described two eye guanylyl cyclases (GC-E and GC-F) that contain an apparent extracellular domain potentially capable of binding ligands (Yang, R.-B., Foster, D. C., Garbers, D. L., and Fülle, H.-J. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 602-606). Here, Northern and Western analyses showed that both cyclases are expressed in the retina and enriched in photoreceptor outer segments. By the use of specific GC-E and GC-F antibodies coupled to different sized gold particles both cyclases were colocalized within the same photoreceptor cells raising the possibility of homomeric and/or heteromeric interactions. A point mutant of GC-E (D878A) was constructed and expressed; it contained no detectable cyclase activity but acted in a dominant negative fashion to abolish the activity of native GC-E and GC-F in coexpression studies. These results suggested that GC-E and GC-F could form either homomers or heteromers, at least when overexpressed in COS-7 cells. Immunoprecipitation with GC-E and GC-F antibody followed by Western analysis confirmed that both homomers and heteromers could be formed. However, similar experiments using retina or outer segments revealed that a vast majority of GC-E and GC-F were precipitated as homomers in the eye. Therefore, like other members of the membrane guanylyl cyclase subfamily, GC-E and GC-F appear to preferentially form homomers.
Asunto(s)
Guanilato Ciclasa/biosíntesis , Células Fotorreceptoras/enzimología , Receptores de Superficie Celular , Receptores de Péptidos/biosíntesis , Animales , Northern Blotting , Células COS , Femenino , Guanilato Ciclasa/química , Guanilato Ciclasa/genética , Peso Molecular , Mutación Puntual , Conformación Proteica , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores de Enterotoxina , Receptores Acoplados a la Guanilato-Ciclasa , Receptores de Péptidos/química , Receptores de Péptidos/genética , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Segmento Externo de la Célula en Bastón/enzimología , SolubilidadRESUMEN
We recently cloned three membrane guanylyl cyclases, designated GC-D, GC-E, and GC-F, from rat olfactory tissue and eye. Amino acid sequence homology suggests that they may compose a new gene subfamily of guanylyl cyclase receptors specifically expressed in sensory tissues. Their chromosomal localization was determined by mouse interspecific backcross analysis. The GC-D, GC-E, and GC-F genes (Gucy2d, Gucy2e, and Gucy2f) are dispersed through the mouse genome in that they map to chromosomes 7, 11, and X, respectively. Close proximity of the mouse GC-D gene to Omp (olfactory marker protein) and Hbb (hemoglobin beta-chain complex) suggests that the human homolog gene maps to 11p15.4 or 11q13.4-q14.1. The human GC-F gene was localized to the long arm of chromosome Xq22 by fluorescence in situ hybridization. The genomic organization of the mouse GC-E gene was determined and compared to other guanylyl cyclase genes. The mouse GC-D, GC-E, and GC-F genomic clones contain identical exon-intron boundaries within their extracellular and cytoplasmic domains, demonstrating the conservation of the gene structures. With respect to human genetic diseases, GC-E mapped to mouse chromosome 11 within a syntenic region on human chromosome 17q13 that has been linked with loci for autosomal dominant retinitis pigmentosa and Leber congenital amaurosis. No apparent disease loci have been yet linked to the locations of the GC-D or GC-F genes.
Asunto(s)
Mapeo Cromosómico , Guanilato Ciclasa/genética , Neuronas Aferentes/metabolismo , Nervio Olfatorio/metabolismo , Retina/metabolismo , Animales , Secuencia de Bases , ADN , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Datos de Secuencia Molecular , Enfermedades de la Retina/genéticaRESUMEN
We have cloned an additional member (GC-D) of the membrane receptor guanylyl cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] family that is specifically expressed in a subpopulation of olfactory sensory neurons. The extracellular, putative ligand-binding domain of the olfactory cyclase is similar in primary structure to two guanylyl cyclases expressed in the retina but diverges considerably from other known guanylyl cyclases. The expression of GC-D RNA is restricted to a small, randomly dispersed population of neurons that is within a single topographic zone in the olfactory neuroepithelium and resembles the pattern of the more diverse seven-transmembrane-domain odorant receptors. These observations suggest that GC-D may function directly in odor recognition or in modulating the sensitivity of a subpopulation of sensory neurons to specific odors.
Asunto(s)
Guanilato Ciclasa/genética , Neuronas Receptoras Olfatorias/enzimología , Receptores de Superficie Celular , Receptores de Péptidos/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Clonación Molecular , Guanilato Ciclasa/biosíntesis , Hibridación in Situ , Datos de Secuencia Molecular , Ratas , Receptores de Enterotoxina , Receptores Acoplados a la Guanilato-Ciclasa , Receptores de Péptidos/biosíntesis , Proteínas Recombinantes/biosíntesis , Análisis de Secuencia de ADN , Distribución TisularRESUMEN
The cDNAs for two membrane guanylyl cyclases, designated E (GC-E) and F (GC-F, were isolated from a rat eye cDNA library. Their deduced topographic structures correspond to known members of the guanylyl cyclase receptor family, containing an extracellular domain, a single membrane-spanning domain, a protein kinase-like domain, and a cyclase catalytic domain. GC-E was expressed in the eye and the pineal gland, whereas GC-F expression was confined to the eye. Overproduction of GC-E and GC-F in COS cells resulted in expression of guanylyl cyclase activity, but ligands known to activate other guanylyl cyclase receptors failed to stimulate enzyme activity. Thus, both GC-E and GC-F remain orphan receptors. Amino acid sequence similarity between GC-E and GC-F in the extracellular region and homology with a cyclase expressed in olfactory neurons and retGC, a rod outer-segment-specific cyclase, suggest that there is another subfamily of guanylyl cyclase receptors, possibly restricted to sensory tissues.
Asunto(s)
Ojo/enzimología , Guanilato Ciclasa/genética , Isoenzimas/genética , Proteínas de la Membrana/genética , Receptores de Superficie Celular , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Clonación Molecular , ADN Complementario/genética , Biblioteca de Genes , Guanilato Ciclasa/biosíntesis , Proteínas de la Membrana/biosíntesis , Membranas/enzimología , Datos de Secuencia Molecular , ARN Mensajero/genética , Ratas , Ratas Sprague-Dawley , Receptores de Enterotoxina , Receptores Acoplados a la Guanilato-Ciclasa , Receptores de Péptidos/genética , Proteínas Recombinantes/biosíntesis , Análisis de Secuencia de ADN , Homología de Secuencia de AminoácidoRESUMEN
There has been no report on changes in mast cells in hepatic radiation injury. Because of the interactions between mast cells and fibroblasts and mast cell changes in radiation interstitial pneumonitis, we examined the mast cells in experimental hepatic irradiation. We used 60Co gamma-ray in a single dose of 10, 30, 50, and 60 Gy given to the liver area of male Wistar rats. The liver tissue was examined 0.5, 1, 2, 3, 6, 9, and 12 months after irradiation. The mast cells were quantitatively and qualitatively assessed in liver sections by light and electronmicroscopy. Typical chronic liver fibrosis occurred after 30 Gy. As the lesions progressed in severity, the number of mast cells increased and they became larger 1 to 2 months after irradiation. After 3 to 6 months, this change was very marked and degranulation was noted. Both the number and size of mast cells were increased markedly. The peak intensity in mast cell changes paralleled that of connective tissue proliferation. At 12 months, when the fibrous tissue was rich in collagen, the mast cells decreased in number. Our findings suggest that mast cells participate in the development of radiation hepatic fibrosis.