RESUMEN
Two isoforms of mammalian cytochrome b5, which have homologous cytosolic amino-terminal catalytic domains, are located one on endoplasmic reticulum (ER b5) the other on mitochondrial outer membranes (OM b5). A cDNA coding for the previously unknown carboxyl-terminal domain of OM b5 was cloned and a chimera between the catalytic domain of ER b5 and the carboxyl-terminal region of OM b5 was expressed in cultured mammalian cells. The chimera localized to mitochondria, indicating that the carboxyl-terminal 43 amino acids of OM b5 contain sufficient information to target the catalytic domain of ER b5 to the mitochondrial outer membrane.
Asunto(s)
Citocromos b5/química , Citocromos b5/metabolismo , Membranas Intracelulares/metabolismo , Mitocondrias/metabolismo , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Sitios de Unión , Línea Celular , Chlorocebus aethiops , Clonación Molecular , Citocromos b5/biosíntesis , Cartilla de ADN , Retículo Endoplásmico/metabolismo , Riñón , Hígado/metabolismo , Mamíferos , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Ratas , Proteínas Recombinantes de Fusión/biosíntesis , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/metabolismo , Homología de Secuencia de Aminoácido , TransfecciónAsunto(s)
Retículo Endoplásmico/metabolismo , Proteínas de Plantas/metabolismo , Plantas/metabolismo , Animales , Transporte Biológico Activo , Sistema Libre de Células , ADN de Plantas/genética , Perros , Técnicas In Vitro , Microsomas/metabolismo , Proteínas de Plantas/genética , Plantas/genética , Plantas/ultraestructura , Plantas Tóxicas , Biosíntesis de Proteínas , Procesamiento Proteico-Postraduccional , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN de Planta/genética , ARN de Planta/metabolismo , Nicotiana/genética , Nicotiana/metabolismo , Transcripción GenéticaRESUMEN
Cytochrome b5 and NADH-cytochrome b5 reductase are integral membrane proteins with cytosolic active domains and short membrane anchors, which are inserted post-translationally into their target membranes. Both are produced as different isoforms, with different localizations, in mammalian cells. In the rat, the reductase gene generates two transcripts by an alternative promoter mechanism: a ubiquitous mRNA coding for the myristylated membrane-bound form, and an erythroid mRNA which generates both the soluble form and a nonmyristylated membrane-binding form. The available evidence indicates that the ubiquitous myristylated form binds to the cytosolic face of both outer mitochondrial membranes and ER. In contrast, two genes code for two homologous forms of cytochrome b5, one of which is found on outer mitochondrial membranes, the other on the ER. The gene specifying the ER form probably also generates an erythroid-specific mRNA by alternative splicing, which codes for soluble cytochrome b5. Possible molecular mechanisms responsible for the observed localizations of these different enzyme isoforms are discussed.
Asunto(s)
Reductasas del Citocromo/metabolismo , Citocromos b5/metabolismo , Retículo Endoplásmico/metabolismo , Procesamiento Proteico-Postraduccional , Animales , Reductasas del Citocromo/genética , Citocromo-B(5) Reductasa , Citocromos b5/genética , Membranas Intracelulares/metabolismo , ARN Mensajero/metabolismoAsunto(s)
Reductasas del Citocromo/metabolismo , Citocromos b5/metabolismo , Retículo Endoplásmico/enzimología , Procesamiento Proteico-Postraduccional , Secuencia de Aminoácidos , Animales , Reductasas del Citocromo/química , Citocromo-B(5) Reductasa , Citocromos b5/química , Humanos , Datos de Secuencia MolecularRESUMEN
A patient with a documented diagnosis of polyarteritis nodosa and laboratory evidence of a circulating lupus anticoagulant is described. Additional clinical features suggestive of the antiphospholipid antibody syndrome were found. The patient underwent amputation of the first two digits of the foot due to ischemic necrosis. Steroid and immunosuppressive treatment resulted in clinical improvement and disappearance of the circulating anticoagulant, without necessitating additional treatment with oral anticoagulants. The presence of the lupus anticoagulant might have worsened the vascular damage done by polyarteritis nodosa in this patient.
Asunto(s)
Autoanticuerpos/análisis , Factores de Coagulación Sanguínea/inmunología , Poliarteritis Nudosa/inmunología , Amputación Quirúrgica , Factores de Coagulación Sanguínea/análisis , Ciclofosfamida/uso terapéutico , Femenino , Humanos , Iloprost/uso terapéutico , Inhibidor de Coagulación del Lupus , Persona de Mediana Edad , Necrosis , Poliarteritis Nudosa/tratamiento farmacológico , Poliarteritis Nudosa/patología , Prednisona/uso terapéutico , Dedos del Pie/patología , Dedos del Pie/cirugíaRESUMEN
We describe a case in which a trisomic 22 placenta could be the cause of severe growth retardation in a chromosomally normal female fetus. At amniocentesis a mosaic 46,XX/47,XX, +22 was observed in amniotic fluid specimens sampled on two different occasions, while fetal blood from a diagnostic cordocentesis revealed a normal chromosome constitution. Postnatal studies showed the consistent presence of trisomic 22 cells in the placenta, while only normal metaphases were found in amnion, blood, and fibroblast cultures.
Asunto(s)
Cromosomas Humanos Par 22 , Retardo del Crecimiento Fetal/etiología , Mosaicismo , Enfermedades Placentarias/complicaciones , Trisomía , Vellosidades Coriónicas/ultraestructura , Femenino , Humanos , Cariotipificación , Persona de Mediana Edad , Enfermedades Placentarias/genética , EmbarazoRESUMEN
Fourteen cases of Essential Mixed Cryoglobulinemia (EMC) are described in this report. Clinical and laboratory manifestations in our patients were similar to those previously reported in literature, although involvement of the peripheral nervous system was much more prevalent in our series. We suggest that peripheral neuropathy should be systematically searched in EMC patients.