scholarly journals Soluble (pro)renin receptor increased by hypoxia maintains oxidative metabolism in trophoblasts

2020 ◽  
Vol 64 (3) ◽  
pp. 145-154 ◽  
Author(s):  
Chikahito Suda ◽  
Junichi Yatabe ◽  
Midori Yatabe ◽  
Miki Yarita ◽  
Atsuhiro Ichihara

Elevated soluble (pro)renin receptor (s(P)RR) concentration in maternal blood is associated with gestational hypertension and preeclampsia. Placenta has abundant expression of (P)RR, and the binding of (P)RR with pyruvate dehydrogenase E1 beta subunit (PDHB) is reported to maintain oxidative metabolism. Thus, we hypothesized that placental hypoxia may increase (P)RR, and the increased (P)RR may preserve PDHB expression. Expression and functional analyses were performed using human placental trophoblast cells, mainly JAR cells. (P)RR co-immunoprecipitated and showed co-immunofluorescence with PDHB mainly in the mitochondria. Hypoxia treatment significantly increased intracellular s(P)RR protein expression, but secreted s(P)RR in the culture medium was decreased by hypoxia. Hypoxia treatment did not alter PDHB expression or activity in the basal condition, but when (P)RR was knocked down by siRNA, PDHB protein and activity were reduced by hypoxia. Acetyl-CoA, the product of PDH activity, was significantly reduced by hypoxia treatment with (P)RR siRNA. S(P)RR is generated from full-length PRR when cleaved by specific proteases. Protease inhibitor experiments suggested furin and site 1 protease as the enzymes generating s(P)RR in JAR cells, and only when treated by site 1 protease inhibitor, PF429242, PDHB protein showed a significant trend to decrease with hypoxia. In JAR cells, hypoxia increased intracellular s(P)RR, and (P)RR preserved the expression and function of PDHB during hypoxia. (P)RR may help maintain oxidative metabolism and efficient energy production during placental ischemia in hypertensive disorders of pregnancy.

2014 ◽  
Vol 5 ◽  
pp. 983-993 ◽  
Author(s):  
Marcelo Rodrigues ◽  
Birgit Lengerer ◽  
Thomas Ostermann ◽  
Peter Ladurner

The use of molecular biology tools in the field of bioadhesion is still in its infancy. For new research groups who are considering taking a molecular approach, the techniques presented here are essential to unravelling the sequence of a gene, its expression and its biological function. Here we provide an outline for addressing adhesion-related genes in diverse organisms. We show how to gradually narrow down the number of candidate transcripts that are involved in adhesion by (1) generating a transcriptome and a differentially expressed cDNA list enriched for adhesion-related transcripts, (2) setting up a BLAST search facility, (3) perform an in situ hybridization screen, and (4) functional analyses of selected genes by using RNA interference knock-down. Furthermore, latest developments in genome-editing are presented as new tools to study gene function. By using this iterative multi-technologies approach, the identification, isolation, expression and function of adhesion-related genes can be studied in most organisms. These tools will improve our understanding of the diversity of molecules used for adhesion in different organisms and these findings will help to develop innovative bio-inspired adhesives.


2000 ◽  
Vol 7 (4) ◽  
pp. 714-716 ◽  
Author(s):  
Adriana Weinberg ◽  
Li Zhang ◽  
Darby Brown ◽  
Alejo Erice ◽  
Bruce Polsky ◽  
...  

ABSTRACT Factors that influence viability and function of cryopreserved peripheral blood mononuclear cells (PBMC) were identified on 54 samples from 27 AIDS Clinical Trial Units. PBMC viability ranged from 1 to 96% with a median of 70%, was higher in laboratories with experienced staff, and was not significantly associated with CD4 cell number. Function of cryopreserved PBMC, measured by lymphocyte proliferation, was associated with viability. Preparations with viability greater than or equal to 70% had consistent proliferative responses and were suitable for functional analyses.


2011 ◽  
Vol 2011 ◽  
pp. 1-15 ◽  
Author(s):  
Andrius Serva ◽  
Christoph Claas ◽  
Vytaute Starkuviene

In the last years miRNAs have increasingly been recognised as potent posttranscriptional regulators of gene expression. Possibly, miRNAs exert their action on virtually any biological process by simultaneous regulation of numerous genes. The importance of miRNA-based regulation in health and disease has inspired research to investigate diverse aspects of miRNA origin, biogenesis, and function. Despite the recent rapid accumulation of experimental data, and the emergence of functional models, the complexity of miRNA-based regulation is still far from being well understood. In particular, we lack comprehensive knowledge as to which cellular processes are regulated by which miRNAs, and, furthermore, how temporal and spatial interactions of miRNAs to their targets occur. Results from large-scale functional analyses have immense potential to address these questions. In this review, we discuss the latest progress in application of high-content and high-throughput functional analysis for the systematic elucidation of the biological roles of miRNAs.


eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Katherine Young Bezold Lamm ◽  
Maddison L Johnson ◽  
Julie Baker Phillips ◽  
Michael B Muntifering ◽  
Jeanne M James ◽  
...  

Healthy pregnancy depends on proper placentation—including proliferation, differentiation, and invasion of trophoblast cells—which, if impaired, causes placental ischemia resulting in intrauterine growth restriction and preeclampsia. Mechanisms regulating trophoblast invasion, however, are unknown. We report that reduction of Inverted formin 2 (INF2) alters intracellular trafficking and significantly impairs invasion in a model of human extravillous trophoblasts. Furthermore, global loss of Inf2 in mice recapitulates maternal and fetal phenotypes of placental insufficiency. Inf2−/− dams have reduced spiral artery numbers and late gestational hypertension with resolution following delivery. Inf2−/− fetuses are growth restricted and demonstrate changes in umbilical artery Doppler consistent with poor placental perfusion and fetal distress. Loss of Inf2 increases fetal vascular density in the placenta and dysregulates trophoblast expression of angiogenic factors. Our data support a critical regulatory role for INF2 in trophoblast invasion—a necessary process for placentation—representing a possible future target for improving placentation and fetal outcomes.


1988 ◽  
Vol 118 (1) ◽  
pp. 68-76 ◽  
Author(s):  
Timo Otonkoski ◽  
Mikael Knip ◽  
Pertti Panula ◽  
Sture Andersson ◽  
Inés Wong ◽  
...  

Abstract. Morphology, yield and function were studied in cultured islet-like cell clusters (ICC) from 140 human fetal pancreata obtained after abortions of different types performed at 11–23 weeks of gestation (12 by hysterotomy, 75 by mechanical dilation and extraction, and 53 induced with prostaglandin). After collagenase digestion and culture in medium supplemented with 10% human serum, up to 2000 free-floating ICC were formed from a single pancreas. Randomly scattered insulin- and glucagon-immunoreactive cells were found in the medullary part of the ICC. More than 100 ICC developed in 100% of the hysterotomies and 87% of the mechanical abortions, but in only 53% of the prostaglandin-induced abortions. Insulin and glucagon levels in the culture medium decreased rapidly during the first 7 days of culture, but then remained stable for at least 31 days. The hysterotomy-derived ICC responded to 10 mmol/l theophylline plus 20 mmol/l glucose by a 12.2 ± 3.1 (sem, N = 7) fold increase in insulin release, as compared with a 5.4 ± 0.9 fold response of the prostaglandin ICC (N = 16; P < 0.02). Despite the low proportion of B-cells, (pro)insulin biosynthesis accounted for 10% of the total protein biosynthesis in low (2 mmol/l) glucose. In conclusion, the yield and viability of the ICC were clearly better, if prostaglandin had not been used for the induction of the abortion.


Microbiology ◽  
2009 ◽  
Vol 155 (8) ◽  
pp. 2546-2559 ◽  
Author(s):  
Emelie Salomonsson ◽  
Åke Forsberg ◽  
Norbert Roos ◽  
Claudia Holz ◽  
Berenike Maier ◽  
...  

Accumulating evidence from a number of studies strongly suggests that proteins orthologous to those involved in type IV pili (Tfp) assembly and function are required for Francisella pathogenicity. However, the molecular mechanisms by which the components exert their influence on virulence remain poorly understood. Owing to the conservation and promiscuity of Tfp biogenesis machineries, expression of Tfp pilins in heterologous species has been used successfully to analyse organelle structure–function relationships. In this study we expressed a number of Francisella pilin genes in the Tfp-expressing pathogen Neisseria gonorrhoeae lacking its endogenous pilin subunit. Two gene products, the orthologous PilA proteins from Francisella tularensis subspecies tularensis and novicida, were capable of restoring the expression of Tfp-like appendages that were shown to be dependent upon the neisserial Tfp biogenesis machinery for surface localization. Expression of Francisella PilA pilins also partially restored competence for natural transformation in N. gonorrhoeae. This phenotype was not complemented by expression of the PulG and XcpT proteins, which are equivalent components of the related type II protein secretion system. Taken together, these findings provide compelling, although indirect, evidence of the potential for Francisella PilA proteins to express functional Tfp.


PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5186 ◽  
Author(s):  
Juan Xiao ◽  
Siyuan Feng ◽  
Xun Wang ◽  
Keren Long ◽  
Yi Luo ◽  
...  

Edible plant-derived exosome-like nanoparticles (EPDELNs) are novel naturally occurring plant ultrastructures that are structurally similar to exosomes. Many EPDELNs have anti-inflammatory properties. MicroRNAs (miRNAs) play a critical role in mediating physiological and pathological processes in animals and plants. Although miRNAs can be selectively encapsulated in extracellular vesicles, little is known about their expression and function in EPDELNs. In this study, we isolated nanovesicles from 11 edible fruits and vegetables and subjected the corresponding EPDELN small RNA libraries to Illumina sequencing. We identified a total of 418 miRNAs—32 to 127 per species—from the 11 EPDELN samples. Target prediction and functional analyses revealed that highly expressed miRNAs were closely associated with the inflammatory response and cancer-related pathways. The 418 miRNAs could be divided into three classes according to their EPDELN distributions: 26 “frequent” miRNAs (FMs), 39 “moderately present” miRNAs (MPMs), and 353 “rare” miRNAs (RMs). FMs were represented by fewer miRNA species than RMs but had a significantly higher cumulative expression level. Taken together, our in vitro results indicate that miRNAs in EPDELNs have the potential to regulate human mRNA.


2021 ◽  
Vol 27 (1) ◽  
pp. 9-11 ◽  
Author(s):  
Gauri Bapayeva ◽  
Milan Terzic ◽  
Karlygash Togyzbayeva ◽  
Aigerim Bekenova ◽  
Sanja Terzic ◽  
...  

Pheochromocytomas are rare tumors producing catecholamines that could be a cause of secondary hypertension. On that basis, pheochromocytoma can occur as an extremely rare cause of hypertension in pregnancy and if diagnosed late can lead to adverse maternal-fetal outcome. In this case report we describe a case of pheochromocytoma affected pregnancy with poor fetal outcome. A 27-year-old pregnant woman was admitted for severe pre-eclampsia due to pre-gestational hypertension that was diagnosed during the first trimester. Due to high and uncontrolled maternal blood pressure and the worsened maternal-fetal condition after the admission induction of fetal lung maturity and emergency cesarean section were performed, but with poor fetal outcome. Later, an adrenal gland mass was identified using abdominal ultrasound and confirmed by computed tomography. After surgical adrenalectomy blood pressure of the patient was normalized. Pheochromocytoma should be considered as a possible cause of hypertensive disorder during pregnancy, particularly in cases of severe and unresponsive hypertension in order to provide for timely and appropriate treatment.


Author(s):  
Purvi M. Parikh ◽  
Vishwa M. Goswami ◽  
Sapana R. Shah ◽  
Rupa C. Vyas ◽  
Hiral Damor

Background: Echocardiography is a safe, non-invasive technique to assess cardiac structure and function in pregnancy. Understanding the structure and function of the heart in hypertensive women is important in terms of timely diagnosis, better management and good prognosis. This study will focus on the importance and feasibility of Echocardiography as a routine investigation tool in hypertensive disorders of pregnancy.Methods: This is a retrospective study of 150 cases of hypertension in pregnancy conducted at the Obstetrics and Gynaecology department of a tertiary care centre in the year June 2019-July 2020. Data was analysed in terms of complications seen in women who had structural and functional abnormalities in the echocardiographic scan in comparison to those hypertensive women who had a normal scan.  The important Echocardiographic parameters were compared amongst cases of hypertension and their impact on fetomaternal outcome was discussed.Results: In this study conducted amongst 150 pregnant women suffering from different forms of hypertensive disorders  presenting in our institute for routine workup in the year 2019-2020, 12(8%) had chronic hypertension, 75(50%) had gestational hypertension, whereas 63(42%) had pre- eclampsia. The incidence of structural valvular lesions in these categories as 2%, 3.34% and 4% respectively. Deranged echocardiographic parameters like decreased Left Ventricular Ejection Fraction in 10%, decreased stroke volume in 28.6% and increased Left Ventricular mass in 26.6% are seen more in cases of pre-eclampsia compared to gestational hypertension and chronic hypertension.Conclusions: Echocardiography is a valuable tool to stratify risk and can guide management in gestational hypertension, chronic hypertension and preeclampsia. Changes in cardiac function and morphology are recognizable at an asymptomatic early stage and correlate with disease severity and adverse outcomes. Preeclampsia has a greater impact on the heart than gestational hypertension, and changes are most pronounced in early onset, severe disease. Studying the cardiac structure and function in early trimesters can bring about better maternal and fetal outcome.


Sign in / Sign up

Export Citation Format

Share Document