Stage-specific Modulation of Neprilysin and Aminopeptidase N in the Limbic System During Kindling Progression

Gortari, Patricia de; Vargas, Miguel; Martínez, Adrián; Vázquez, Arlene Iskra García; Uribe, R.M.; Chávez‐Gutiérrez, Lucía; Magdaleno, V. M.; Boileau, Guy; Charlí, Jean-Louis; Joseph‐Bravo, Patricia

doi:10.1007/s12031-007-0020-9

Cited by 5 publications

(2 citation statements)

References 63 publications

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“…1 ). Mme has been studied in renal, lung and neural tissues, however, very little is known about its role in the placenta [ 33 ]. SNPs leading to truncations of the Mme gene and the loss of neutral endopeptidase (NEP) protein are theorised to be the cause for allo-immunisation during pregnancy [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

The rat placental renin-angiotensin system - a gestational gene expression study

Vaswani

Chan

Verma

et al. 2015

Reprod Biol Endocrinol

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BackgroundThe placenta is an essential organ that provides nutrients and oxygen to the developing fetus and removes toxic waste products from the fetal circulation. Maintaining placental blood osmotic pressure and blood flow is crucial for viable offspring. The renin-angiotensin system (RAS) in the placenta is a key player in the regulation of maternal-fetal blood flow during pregnancy. Therefore, the aim of this study was to determine if RAS genes are differentially expressed in mid to late gestation in rat placenta.MethodsWhole placental tissue samples from pregnant Sprague Dawley rats at embryonic (E) days 14.25, 15.25, 17.25 and 20 (n = 6 for each gestational age) were used for genome-wide gene expression by microarray. RAS genes with expression differences of >2 fold were further analyzed. Quantitative Real-Time PCR (qPCR) was performed on independent samples to confirm and validate microarray data. Immunohistochemisty and Western blotting were performed on a differentially expressed novel RAS pathway gene (ANPEP).ResultsSix out of 17 genes of the RAS pathway were differentially expressed at different gestational ages. Gene expression of four genes (Angiotensin converting enzyme (Ace), angiotensin converting enzyme 2 (Ace2), membrane metalloendopeptidase (Mme) and angiotensin II receptor 1A (Agtr1a)) were significantly upregulated at E20 whereas two others (Thimet oligopeptidase 1 (Thop1) and Alanyl aminopeptidase (Anpep)) were downregulated at E20 prior to the onset of labour. These changes were confirmed by qPCR. Western blots revealed no overall differences in ANPEP protein expression in the placentae. Immunohistochemical studies, however, indicated that the localization of ANPEP differed at E17.25 and E20 as ANPEP localization in the giant trophoblast cell of the junctional zone was no longer detectable at E20.ConclusionsThe current study investigated the expression of members of the RAS pathway in rat placentae and observed significantly altered expression of 6 RAS genes at 4 gestational ages. These findings present the need for further comprehensive investigation of RAS genes in normal and complicated pregnancies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12958-015-0088-y) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

The rat placental renin-angiotensin system - a gestational gene expression study

Vaswani

Chan

Verma

et al. 2015

Reprod Biol Endocrinol

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“…The reaction rate and the ectoenzyme activity can then be estimated [50, 61–67]. It is also informative to examine changes in translational precursors (mRNAs) to determine changes in ectoenzyme synthesis, using reverse-transcription polymerase chain reaction (RT-PCR), northern blot, and in-situ hybridization coupled to immunohistochemistry [68–70]. We are not aware of methods other than ours for determining ectoenzyme levels in intact tissue.…”

Section: Introductionmentioning

confidence: 99%

Electroosmotic perfusion of tissue: sampling the extracellular space and quantitative assessment of membrane-bound enzyme activity in organotypic hippocampal slice cultures

Sandberg

et al. 2014

Anal Bioanal Chem

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This review covers recent advances in sampling fluid from the extracellular space of brain tissue by electroosmosis (EO). Two techniques, EO sampling with a single fused-silica capillary and EO push–pull perfusion, have been developed. These tools were used to investigate the function of membrane-bound enzymes with outward-facing active sites, or ectoenzymes, in modulating the activity of the neuropeptides leu-enkephalin and galanin in organotypic-hippocampal-slice cultures (OHSCs). In addition, the approach was used to determine the endogenous concentration of a thiol, cysteamine, in OHSCs. We have also investigated the degradation of coenzyme A in the extracellular space. The approach provides information on ectoenzyme activity, including Michaelis constants, in tissue, which, as far as we are aware, has not been done before. On the basis of computational evidence, EO push–pull perfusion can distinguish ectoenzyme activity with a ~100 µm spatial resolution, which is important for studies of enzyme kinetics in adjacent regions of the rat hippocampus.

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Acute Ethanol Administration Differentially Alters Enkephalinase and Aminopeptidase N Activity and mRNA Levels in Regions of the Nigrostriatal Pathway

et al. 2012

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Opioid peptides play a key role in ethanol reinforcement and may also represent important determinants in brain sensitivity to ethanol through modulation of nigrostriatal dopaminergic activity. Regulation of opioid levels by peptidase-degrading enzymes could be relevant in ethanol's actions. The aim of this work was to study the acute ethanol (2.5 g/kg) effects on the activity and mRNA expression of enkephalinase (NEP) and aminopeptidase N (APN) in the rat substantia nigra (SN) and the anterior-medial (amCP) and medial-posterior (mpCP) regions of the caudate-putamen (CP). Enzymatic activities were measured by fluorometric assays and mRNA expression by reverse transcriptase polymerase chain reaction. Acute ethanol administration differentially altered peptidase activities and mRNA expression with different kinetics. Ethanol increased and decreased NEP mRNA levels in the SN and amCP, respectively, but produced biphasic effects in the mpCP. APN mRNA levels were increased by ethanol in all brain regions. Ethanol induced a transient and long-lasting increase in NEP (mpCP) and APN (amCP) activities, respectively. Peptidase activities were not changed by ethanol in the SN. Our results indicate that striatal NEP and APN are important ethanol targets. Ethanol-induced changes in these neuropeptidases in the CP could contribute to the mechanisms involved in brain sensitivity to ethanol.

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Stage-specific Modulation of Neprilysin and Aminopeptidase N in the Limbic System During Kindling Progression

Cited by 5 publications

References 63 publications

The rat placental renin-angiotensin system - a gestational gene expression study

The rat placental renin-angiotensin system - a gestational gene expression study

Electroosmotic perfusion of tissue: sampling the extracellular space and quantitative assessment of membrane-bound enzyme activity in organotypic hippocampal slice cultures

Acute Ethanol Administration Differentially Alters Enkephalinase and Aminopeptidase N Activity and mRNA Levels in Regions of the Nigrostriatal Pathway

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