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1.
BMC Med Genet ; 12: 64, 2011 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-21569342

RESUMEN

BACKGROUND: Preeclampsia affects 3-8% of pregnancies and is a major cause of maternal and perinatal morbidity and mortality worldwide. This complex disorder is characterized by alterations in the immune and vascular systems and involves multiple organs. There is strong evidence for a genetic contribution to preeclampsia. Two different single nucleotide polymorphisms (SNPs) in the endoplasmic reticulum aminopeptidase 2 (ERAP2) gene were recently reported to be associated with increased risk for preeclampsia in two different populations. ERAP2 is expressed in placental tissue and it is involved in immune responses, inflammation, and blood pressure regulation; making it is an attractive preeclampsia candidate gene. Furthermore, ERAP2 expression is altered in first trimester placentas of women destined to develop preeclampsia. METHODS: A case-control design was used to test for associations between two SNPs in ERAP2, rs2549782 and rs17408150, and preeclampsia status in 1103 Chilean maternal-fetal dyads and 1637 unpaired African American samples (836 maternal, 837 fetal). RESULTS: We found that the fetal minor allele (G) of rs2549782 was associated with an increased risk for preeclampsia in the African American population (P = 0.009), but not in the Chilean population. We found no association between rs17408150 and risk for preeclampsia in the Chilean population. Association between rs17408150 and risk for preeclampsia was not tested in the African American population due to the absence of the minor allele in this population. CONCLUSIONS: We report an association between fetal ERAP2 and preeclampsia in an African American population. In conjunction with previous studies, which have found maternal associations with this gene in an Australian/New Zealand population and a Norwegian population, ERAP2 has now been associated with preeclampsia in three populations. This provides strong evidence that ERAP2 plays a role in the development of preeclampsia.


Asunto(s)
Aminopeptidasas/genética , Negro o Afroamericano/genética , Feto/enzimología , Polimorfismo de Nucleótido Simple/genética , Preeclampsia/genética , Adulto , Estudios de Casos y Controles , Chile , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad/genética , Humanos , Masculino , Embarazo
2.
J Cell Biochem ; 105(3): 703-11, 2008 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-18680145

RESUMEN

Angiotensin II (Ang II) AT(2) receptors are abundantly expressed in rat fetal tissues where they probably contribute to development. In the present study we examine the effects of Ang II type 2 receptor stimulation on SHP-1 activation. Ang II (10(-7) M) elicits a rapid and transient tyrosine phosphorylation of SHP-1, maximal at 1 min, in a dose-dependent form, blocked by the AT(2) antagonist, PD123319. SHP-1 phosphorylation is followed in time by tyrosine dephosphorylation of different proteins, suggesting a sequence of events. Ang II induces association of SHP-1 to AT(2) receptors as shown by co-immunoprecipitation, Western blot and binding assays. SHP-1 activity was determined in immunocomplexes obtained with either anti-AT(2) or anti-SHP-1 antibodies, after Ang II stimulation (1 min), in correlation with the maximal level of SHP-1 phosphorylation. Interestingly, following receptor stimulation (1 min) c-Src was associated to AT(2) or SHP-1 immunocomplexes. Preincubation with the c-Src inhibitor PP2 inhibited SHP-1 activation and c-Src association, thus confirming the participation of c-Src in this pathway. We demonstrated here for the first time the involvement of c-Src in SHP-1 activation via AT(2) receptors present in an ex vivo model expressing both receptor subtypes. In this model, AT(2) receptors are not constitutively associated to SHP-1 and SHP-1 is not constitutively activated. Thus, we clearly establish that SHP-1 activation, mediated by the AT(2) subtype, involves c-Src and precedes protein tyrosine dephosphorylation, in rat fetal membranes.


Asunto(s)
Feto/enzimología , Proteína Tirosina Fosfatasa no Receptora Tipo 6/metabolismo , Proteínas Proto-Oncogénicas pp60(c-src)/metabolismo , Receptor de Angiotensina Tipo 2/metabolismo , Animales , Femenino , Fosforilación , Ratas , Ratas Wistar , Transducción de Señal
3.
J Mol Histol ; 39(2): 217-25, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18034316

RESUMEN

Quiescin Q6/sulfhydryl oxidases (QSOX) are revisited thiol oxidases considered to be involved in the oxidative protein folding, cell cycle control and extracellular matrix remodeling. They contain thioredoxin domains and introduce disulfide bonds into proteins and peptides, with the concomitant hydrogen peroxide formation, likely altering the redox environment. Since it is known that several developmental processes are regulated by the redox state, here we assessed if QSOX could have a role during mouse fetal development. For this purpose, an anti-recombinant mouse QSOX antibody was produced and characterized. In E(13.5), E(16.5) fetal tissues, QSOX immunostaining was confined to mesoderm- and ectoderm-derived tissues, while in P1 neonatal tissues it was slightly extended to some endoderm-derived tissues. QSOX expression, particularly by epithelial tissues, seemed to be developmentally-regulated, increasing with tissue maturation. QSOX was observed in loose connective tissues in all stages analyzed, intra and possibly extracellularly, in agreement with its putative role in oxidative folding and extracellular matrix remodeling. In conclusion, QSOX is expressed in several tissues during mouse development, but preferentially in those derived from mesoderm and ectoderm, suggesting it could be of relevance during developmental processes.


Asunto(s)
Feto/enzimología , Oxidorreductasas/metabolismo , Animales , Animales Recién Nacidos , Especificidad de Anticuerpos , Inmunohistoquímica , Masculino , Ratones , Oxidorreductasas/análisis , Oxidorreductasas/inmunología , Conejos , Ratas , Ratas Wistar , Distribución Tisular
4.
Reproduction ; 134(4): 605-13, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17890296

RESUMEN

Matrix metalloproteinases (MMPs) play an important role in tissue remodeling that accompanies the rapid growth, differentiation, and structural changes of the placenta and several fetal organs. In the present study, we investigated whether the diabetic maternal environment may alter the regulatory homeostasis exerted by nitric oxide (NO) on MMPs activity in the feto-placental unit from rats at midgestation. We found that NADPH-diaphorase activity, which reflects the distribution and activity of NO synthases (NOS), was increased in both placenta and fetuses from diabetic rats when compared with controls. In addition, while a NO donor enhanced MMP2 and MMP9 activities, a NOS inhibitor reduced these activities in the maternal side of the placenta from control rats. This regulatory effect of NO was only observed on MMP9 in the diabetic group. On the other hand, the NO donor did not modify MMP2 and MMP9 activities, while the NOS inhibitor reduced MMP9 activity in the fetal side of both control and diabetic placentas. In the fetuses, MMP2 was enhanced by the NO donor and reduced by the NO inhibitor in both fetuses from control and diabetic rats. Overall, this study demonstrates that NO is able to modulate the activation of MMPs in the feto-placental unit, and provides supportive evidence that increased NOS activity leads to NO overproduction in the feto-placental unit from diabetic rats, an alteration closely related to the observed MMPs dysregulation that may have profound implications in the formation and function of the placenta and the fetal organs.


Asunto(s)
Diabetes Mellitus Experimental/metabolismo , Feto/enzimología , Metaloproteinasas de la Matriz/metabolismo , Óxido Nítrico/fisiología , Placenta/enzimología , Animales , Western Blotting/métodos , Electroforesis en Gel de Poliacrilamida , Femenino , Feto/efectos de los fármacos , Metaloproteinasa 2 de la Matriz/análisis , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/análisis , Metaloproteinasa 9 de la Matriz/metabolismo , Metaloproteinasas de la Matriz/análisis , NG-Nitroarginina Metil Éster/farmacología , Donantes de Óxido Nítrico/farmacología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II/análisis , Óxido Nítrico Sintasa de Tipo III/análisis , Nitroprusiato/farmacología , Placenta/efectos de los fármacos , Embarazo , Ratas , Ratas Wistar
5.
Free Radic Res ; 39(12): 1285-93, 2005 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-16298858

RESUMEN

Maternal diabetes increases the risk of congenital malformations, placental dysfunction and diseases in both the neonate and the offspring's later life. Oxidative stress has been involved in the etiology of these abnormalities. Matrix metalloproteases (MMPs), involved in multiple developmental pathways, are increased in the fetus and placenta from diabetic experimental models. As oxidants could be involved in the activation of latent MMPs, we investigated a putative relationship between MMPs activities and oxidative stress in the feto-placental unit of diabetic rats at midgestation. We found that H2O2 enhanced and that superoxide dismutase (SOD) reduced MMPs activities in the maternal side of the placenta and in the fetuses from control and diabetic rats. MMPs were not modified by oxidative status in the fetal side of the placenta. Lipid peroxidation was enhanced in the maternal and fetal sides of the placenta and in the fetus from diabetic rats when compared to controls, and gradually decreased from the maternal placental side to the fetus in diabetic animals. The activities of the antioxidant enzymes SOD and catalase were decreased in the maternal placental side, catalase activity was enhanced in the fetal placental side and both enzymes were increased in the fetuses from diabetic rats when compared to controls. Our data demonstrate changes in the oxidative balance and capability of oxidants to upregulate MMPs activity in the feto-placental unit from diabetic rats, a basis to elucidate links between oxidative stress and alterations in the developmental pathways in which MMPs are involved.


Asunto(s)
Diabetes Mellitus Experimental/metabolismo , Feto/metabolismo , Metaloproteinasa 2 de la Matriz/biosíntesis , Metaloproteinasa 9 de la Matriz/biosíntesis , Estrés Oxidativo , Placenta/metabolismo , Embarazo en Diabéticas/metabolismo , Animales , Catalasa/metabolismo , Diabetes Mellitus Experimental/enzimología , Femenino , Feto/enzimología , Peroxidación de Lípido , Placenta/enzimología , Embarazo , Embarazo en Diabéticas/enzimología , Ratas , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismo , Regulación hacia Arriba
6.
Histochem J ; 24(12): 964-8, 1992 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-1362719

RESUMEN

A portion of consistently gamma-glutamyl transpeptidase-positive epithelium in the normal oral mucosa of rats is described. This is the first normal oral mucosa epithelium reported to express activity of the transpeptidase. This enzyme has been used as a marker of malignant transformation in tissues such as epidermis and oral mucosa epithelium. Complementary studies of the enzyme-positive portion of oral mucosa and a neighbouring negative portion, suggest that, in this model, expression of gamma-glutamyl transpeptidase is linked to a terminally-differentiated epithelium.


Asunto(s)
Mucosa Bucal/enzimología , gamma-Glutamiltransferasa/metabolismo , Animales , Biomarcadores de Tumor , Transformación Celular Neoplásica , Epitelio/enzimología , Epitelio/crecimiento & desarrollo , Feto/enzimología , Histocitoquímica , Mucosa Bucal/crecimiento & desarrollo , Ratas , Ratas Wistar
7.
Biol Neonate ; 59(5): 294-302, 1991.
Artículo en Inglés | MEDLINE | ID: mdl-1908323

RESUMEN

Glycogen content and the enzymes of glycogen metabolism have been measured in the postimplantation rat embryo over a period ranging from 9.5 to 18.5 days of gestation. The earliest periods studied were at days 9.5 and 10.5 of gestation, when the yolk sac becomes vascularized and heart beat is first established. The next intervals were at days 10.5-11.5 when vascular connections via the allantoic placenta are formed. At 14.5 and 18.5 days of development, 4 entire organs were analyzed; heart, liver, kidney and brain. The metabolic apparatus of glycogen metabolism was concentrated in the embryo at 10.5 days, then the heart region, and in the heart itself at later stages.


Asunto(s)
Embrión de Mamíferos/metabolismo , Feto/metabolismo , Glucógeno Sintasa/metabolismo , Glucógeno/metabolismo , Fosforilasas/metabolismo , Animales , Embrión de Mamíferos/enzimología , Femenino , Feto/enzimología , Edad Gestacional , Especificidad de Órganos , Embarazo , Ratas , Ratas Endogámicas
8.
J Pediatr ; 113(3): 463-8, 1988 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-2900886

RESUMEN

The expression and activity of phenylalanine hydroxylase was studied in the liver of a fetus aborted after prenatal diagnosis of phenylketonuria. No phenylalanine hydroxylase enzymatic activity or immunoreactive protein was detectable in the PKU liver specimen, though both enzymatic activity and immunoreactive protein were detectable in control specimens of similar gestational age. Phenylalanine hydroxylase messenger RNA of normal size was present in the PKU fetal liver at normal abundance. These results confirm the genetic diagnosis of PKU in this fetus and indicate that the mutations in this fetus affect translation or stability of the phenylalanine hydroxylase protein.


Asunto(s)
Hígado/enzimología , Fenilalanina Hidroxilasa/metabolismo , Fenilcetonurias/enzimología , Aborto Inducido , Femenino , Feto/enzimología , Humanos , Recién Nacido , Hígado/embriología , Fenilalanina Hidroxilasa/genética , Fenilcetonurias/diagnóstico , Fenilcetonurias/genética , Polimorfismo de Longitud del Fragmento de Restricción , Embarazo , Diagnóstico Prenatal
9.
J Pediatr ; 110(1): 106-10, 1987 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-3794868

RESUMEN

We examined the chronology of development of both fetal lung antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) and disaturated phosphatidylcholine ("surfactant") during late gestation in four laboratory animal species: rat, rabbit, hamster, and guinea pig. An essentially similar pattern of prenatal biochemical maturation was found in all four species. The developmental changes were characterized by (1) rapid elevations in fetal lung antioxidant enzyme levels during the final 10% to 15% of gestation, and (2) an essentially parallel rapid rise in lung surfactant content during the final 10% to 15% of gestation. The increase in the lung activity of the individual antioxidant enzymes prior to birth averaged approximately 150% to 200%. Our findings suggest that late gestational changes in the principal pulmonary antioxidant defense system (like the changes in the surfactant system) represents a normal "preparation for birth," required to assure successful functioning of the neonatal lung in the relatively oxygen-rich ex utero environment.


Asunto(s)
Feto/enzimología , Pulmón/enzimología , Mamíferos/metabolismo , Animales , Cricetinae , Madurez de los Órganos Fetales , Edad Gestacional , Cobayas , Humanos , Pulmón/embriología , Mamíferos/embriología , Oxidación-Reducción , Fosfatidilcolinas/biosíntesis , Conejos , Ratas
12.
J Pediatr ; 106(3): 417-20, 1985 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-3973779

RESUMEN

A child with triose phosphate isomerase deficiency has congenital nonspherocytic hemolytic anemia, mental subnormality, motor impairment, growth failure, and cardiac failure. The deficiency state is characterized by moderately reduced red cell triose phosphate isomerase activity and marked instability of the abnormal enzyme to heat. The stability characteristics of triose phosphate isomerase in cultured fibroblasts define the homozygous and heterozygous states with sufficient precision to allow prenatal diagnosis of the disorder. Successful prenatal identification of a heterozygote and an unaffected fetus in utero is described.


Asunto(s)
Anemia Hemolítica Congénita no Esferocítica/enzimología , Anemia Hemolítica Congénita/enzimología , Carbohidrato Epimerasas/deficiencia , Diagnóstico Prenatal , Triosa-Fosfato Isomerasa/deficiencia , Amniocentesis , Células Cultivadas , Eritrocitos/enzimología , Femenino , Feto/enzimología , Fibroblastos/enzimología , Calor , Humanos , Masculino , Linaje , Embarazo , Talasemia/enzimología , Talasemia/genética
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