oalib

Publish in OALib Journal

ISSN: 2333-9721

APC: Only $99

Submit

Any time

2019 ( 186 )

2018 ( 312 )

2017 ( 314 )

2016 ( 427 )

Custom range...

Search Results: 1 - 10 of 230476 matches for " Simon C Langley-Evans "
All listed articles are free for downloading (OA Articles)
Page 1 /230476
Display every page Item
Mitochondrial Respiration Is Decreased in Rat Kidney Following Fetal Exposure to a Maternal Low-Protein Diet
Sarah Engeham,Kennedy Mdaki,Kirsty Jewell,Ruth Austin,Alexander N. Lehner,Simon C. Langley-Evans
Journal of Nutrition and Metabolism , 2012, DOI: 10.1155/2012/989037
Abstract: Maternal protein restriction in rat pregnancy is associated with impaired renal development and age-related loss of renal function in the resulting offspring. Pregnant rats were fed either control or low-protein (LP) diets, and kidneys from their male offspring were collected at 4, 13, or 16 weeks of age. Mitochondrial state 3 and state 4 respiratory rates were decreased by a third in the LP exposed adults. The reduction in mitochondrial function was not explained by complex IV deficiency or altered expression of the complex I subunits that are typically associated with mitochondrial dysfunction. Similarly, there was no evidence that LP-exposure resulted in greater oxidative damage to the kidney, differential expression of ATP synthetase β-subunit, and ATP-ADP translocase 1. mRNA expression of uncoupling protein 2 was increased in adult rats exposed to LP in utero, but there was no evidence of differential expression at the protein level. Exposure to maternal undernutrition is associated with a decrease in mitochondrial respiration in kidneys of adult rats. In the absence of gross disturbances in respiratory chain protein expression, programming of coupling efficiency may explain the long-term impact of the maternal diet.
The Effects of Prenatal Protein Restriction on -Adrenergic Signalling of the Adult Rat Heart during Ischaemia Reperfusion
Kevin J. P. Ryan,Matthew J. Elmes,Simon C. Langley-Evans
Journal of Nutrition and Metabolism , 2012, DOI: 10.1155/2012/397389
Abstract: A maternal low-protein diet (MLP) fed during pregnancy leads to hypertension in adult rat offspring. Hypertension is a major risk factor for ischaemic heart disease. This study examined the capacity of hearts from MLP-exposed offspring to recover from myocardial ischaemia-reperfusion (IR) and related this to cardiac expression of β-adrenergic receptors (β-AR) and their associated G proteins. Pregnant rats were fed control (CON) or MLP diets (=12 each group) throughout pregnancy. When aged 6 months, hearts from offspring underwent Langendorff cannulation to assess contractile function during baseline perfusion, 30 min ischemia and 60 min reperfusion. CON male hearts demonstrated impaired recovery in left ventricular pressure (LVP) and /max (<0.01) during reperfusion when compared to MLP male hearts. Maternal diet had no effect on female hearts to recover from IR. MLP males exhibited greater membrane expression of β2-AR following reperfusion and urinary excretion of noradrenaline and dopamine was lower in MLP and CON female rats versus CON males. In conclusion, the improved cardiac recovery in MLP male offspring following IR was attributed to greater membrane expression of β2-AR and reduced noradrenaline and dopamine levels. In contrast, females exhibiting both decreased membrane expression of β2-AR and catecholamine levels were protected from IR injury.
Cell Cycle Regulation and Cytoskeletal Remodelling Are Critical Processes in the Nutritional Programming of Embryonic Development
Angelina Swali, Sarah McMullen, Helen Hayes, Lorraine Gambling, Harry J. McArdle, Simon C. Langley-Evans
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0023189
Abstract: Many mechanisms purport to explain how nutritional signals during early development are manifested as disease in the adult offspring. While these describe processes leading from nutritional insult to development of the actual pathology, the initial underlying cause of the programming effect remains elusive. To establish the primary drivers of programming, this study aimed to capture embryonic gene and protein changes in the whole embryo at the time of nutritional insult rather than downstream phenotypic effects. By using a cross-over design of two well established models of maternal protein and iron restriction we aimed to identify putative common “gatekeepers” which may drive nutritional programming. Both protein and iron deficiency in utero reduced the nephron complement in adult male Wistar and Rowett Hooded Lister rats (P<0.05). This occurred in the absence of damage to the glomerular ultrastructure. Microarray, proteomic and pathway analyses identified diet-specific and strain-specific gatekeeper genes, proteins and processes which shared a common association with the regulation of the cell cycle, especially the G1/S and G2/M checkpoints, and cytoskeletal remodelling. A cell cycle-specific PCR array confirmed the down-regulation of cyclins with protein restriction and the up-regulation of apoptotic genes with iron deficiency. The timing and experimental design of this study have been carefully controlled to isolate the common molecular mechanisms which may initiate the sequelae of events involved in nutritional programming of embryonic development. We propose that despite differences in the individual genes and proteins affected in each strain and with each diet, the general response to nutrient deficiency in utero is perturbation of the cell cycle, at the level of interaction with the cytoskeleton and the mitotic checkpoints, thereby diminishing control over the integrity of DNA which is allowed to replicate. These findings offer novel insight into the primary causes and mechanisms leading to the pathologies which have been identified by previous programming studies.
Processes Underlying the Nutritional Programming of Embryonic Development by Iron Deficiency in the Rat
Angelina Swali, Sarah McMullen, Helen Hayes, Lorraine Gambling, Harry J. McArdle, Simon C. Langley-Evans
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0048133
Abstract: Poor iron status is a global health issue, affecting two thirds of the world population to some degree. It is a particular problem among pregnant women, in both developed and developing countries. Feeding pregnant rats a diet deficient in iron is associated with both hypertension and reduced nephron endowment in adult male offspring. However, the mechanistic pathway leading from iron deficiency to fetal kidney development remains elusive. This study aimed to establish the underlying processes associated with iron deficiency by assessing gene and protein expression changes in the rat embryo, focussing on the responses occurring at the time of the nutritional insult. Analysis of microarray data showed that iron deficiency in utero resulted in the significant up-regulation of 979 genes and down-regulation of 1545 genes in male rat embryos (d13). Affected processes associated with these genes included the initiation of mitosis, BAD-mediated apoptosis, the assembly of RNA polymerase II preinitiation complexes and WNT signalling. Proteomic analyses highlighted 7 proteins demonstrating significant up-regulation with iron deficiency and the down-regulation of 11 proteins. The main functions of these key proteins included cell proliferation, protein transport and folding, cytoskeletal remodelling and the proteasome complex. In line with our recent work, which identified the perturbation of the proteasome complex as a generalised response to in utero malnutrition, we propose that iron deficiency alone leads to a more specific failure in correct protein folding and transport. Such an imbalance in this delicate quality-control system can lead to cellular dysfunction and apoptosis. Therefore these findings offer an insight into the underlying mechanisms associated with the development of the embryo during conditions of poor iron status, and its health in adult life.
The impact of maternal protein restriction during rat pregnancy upon renal expression of angiotensin receptors and vasopressin-related aquaporins
Ruth Cornock, Simon C Langley-Evans, Ali Mobasheri, Sarah McMullen
Reproductive Biology and Endocrinology , 2010, DOI: 10.1186/1477-7827-8-105
Abstract: Female Wistar rats were mated and fed a control (18% casein) or low-protein (9% casein) diet during pregnancy. Animals were anaesthetised on days 5, 10, 15 and 20 of gestation (n = 8/group/time-point) for determination of plasma volume using Evans Blue dye, prior to euthanasia and collection of tissues. Expression of the ATR subtypes and AQP2, 3 and 4 were assessed in maternal kidneys by PCR and western blotting. 24 non-pregnant Wistar rats underwent the same procedure at defined points of the oestrous cycle.As expected, pregnancy was associated with an increase in blood volume and haemodilution impacted upon red blood cell counts and haemoglobin concentrations. Expression of angiotensin II receptors and aquaporins 2, 3 and 4 was stable across all stages of the oestrus cycle. Interesting patterns of intra-renal protein expression were observed in response to pregnancy, including a significant down-regulation of AQP2. In contrast to previous literature and despite an apparent delay in blood volume expansion in low-protein fed rats, blood volume did not differ significantly between groups of pregnant animals. However, a significant down-regulation of AT2R protein expression was observed in low-protein fed animals alongside a decrease in creatinine clearance.Regulatory systems involved in the pregnancy-induced plasma volume expansion are susceptible to the effects of maternal protein restriction.Human pregnancy is associated with a 30-50% increase in plasma volume, beginning early in the first trimester and peaking at around 32 weeks of gestation [1]. Coupled with an expansion of red blood cell mass, this leads to an increase in blood volume [2]. Failure to expand circulating volume is associated with intrauterine growth restriction and hypertensive complications of pregnancy [1,3,4]. A similar profile of plasma volume expansion occurs in rodents during pregnancy [5], providing a useful model with which to examine the molecular and physiological mechanisms of volume ex
Developmental Origins of Health and Disease
Simon C. Langley-Evans,Barbara Alexander,Harry J. McArdle,Deborah M. Sloboda
Journal of Nutrition and Metabolism , 2012, DOI: 10.1155/2012/838640
Abstract:
Developmental Origins of Health and Disease
Simon C. Langley-Evans,Barbara Alexander,Harry J. McArdle,Deborah M. Sloboda
Journal of Nutrition and Metabolism , 2012, DOI: 10.1155/2012/838640
Abstract:
Mitochondrial Respiration Is Decreased in Rat Kidney Following Fetal Exposure to a Maternal Low-Protein Diet
Sarah Engeham,Kennedy Mdaki,Kirsty Jewell,Ruth Austin,Alexander N. Lehner,Simon C. Langley-Evans
Journal of Nutrition and Metabolism , 2012, DOI: 10.1155/2012/989037
Abstract: Maternal protein restriction in rat pregnancy is associated with impaired renal development and age-related loss of renal function in the resulting offspring. Pregnant rats were fed either control or low-protein (LP) diets, and kidneys from their male offspring were collected at 4, 13, or 16 weeks of age. Mitochondrial state 3 and state 4 respiratory rates were decreased by a third in the LP exposed adults. The reduction in mitochondrial function was not explained by complex IV deficiency or altered expression of the complex I subunits that are typically associated with mitochondrial dysfunction. Similarly, there was no evidence that LP-exposure resulted in greater oxidative damage to the kidney, differential expression of ATP synthetase β-subunit, and ATP-ADP translocase 1. mRNA expression of uncoupling protein 2 was increased in adult rats exposed to LP in utero, but there was no evidence of differential expression at the protein level. Exposure to maternal undernutrition is associated with a decrease in mitochondrial respiration in kidneys of adult rats. In the absence of gross disturbances in respiratory chain protein expression, programming of coupling efficiency may explain the long-term impact of the maternal diet. 1. Introduction Retrospective associations between low weight or thinness at birth and risk of cardiovascular disease and type 2 diabetes gave rise to the hypothesis that maternal nutritional status may be one of a number of factors that programme long-term risk of disease [1–4].This hypothesis has received strong support from studies of small and large animal species, which overwhelmingly indicate that exposure to undernutrition in pregnancy, whether specific to macronutrients [5] or micronutrients (e.g., iron) [6], or in the form of lower overall food intake [7], programmes risk of adult hypertension, glucose intolerance, insulin resistance, and dyslipidaemia [5–9].Maternal protein restriction during rat pregnancy has been widely reported to impact upon blood pressure in the exposed offspring and the hypertension observed in such animals has partly been linked to programming of renal development [10]. Maternal protein restriction brings about early-life programming through remodelling of specific tissues [11]. In the kidney, the number of nephrons is reduced through exposure to maternal undernutrition, and with ageing, low-protein-exposed animals develop glomerular injury and progressive loss of renal function [10, 12, 13]. There is evidence to suggest that this is, at least in part, mediated by decreased activity of antioxidant
Glucocorticoid Effects on the Programming of AT1b Angiotensin Receptor Gene Methylation and Expression in the Rat
Irina Bogdarina,Andrea Haase,Simon Langley-Evans,Adrian J. L. Clark
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0009237
Abstract: Adverse events in pregnancy may ‘programme’ offspring for the later development of cardiovascular disease and hypertension. Previously, using a rodent model of programmed hypertension we have demonstrated the role of the renin-angiotensin system in this process. More recently we showed that a maternal low protein diet resulted in undermethylation of the At1b angiotensin receptor promoter and the early overexpression of this gene in the adrenal of offspring. Here, we investigate the hypothesis that maternal glucocorticoid modulates this effect on fetal DNA methylation and gene expression. We investigated whether treatment of rat dams with the 11β-hydroxylase inhibitor metyrapone, could prevent the epigenetic and gene expression changes we observed. Offspring of mothers subjected to a low protein diet in pregnancy showed reduced adrenal Agtr1b methylation and increased adrenal gene expression as we observed previously. Treatment of mothers with metyrapone for the first 14 days of pregnancy reversed these changes and prevented the appearance of hypertension in the offspring at 4 weeks of age. As a control for non-specific effects of programmed hypertension we studied offspring of mothers treated with dexamethasone from day 15 of pregnancy and showed that, whilst they had raised blood pressure, they failed to show any evidence of Agtr1b methylation or increase in gene expression. We conclude that maternal glucocorticoid in early pregnancy may induce changes in methylation and expression of the Agtr1b gene as these are clearly reversed by an 11 beta-hydroxylase inhibitor. However in later pregnancy a converse effect with dexamethasone could not be demonstrated and this may reflect either an alternative mechanism of this glucocorticoid or a stage-specific influence.
Genome-Wide Methylation and Gene Expression Changes in Newborn Rats following Maternal Protein Restriction and Reversal by Folic Acid
Gioia Altobelli, Irina G. Bogdarina, Elia Stupka, Adrian J. L. Clark, Simon Langley-Evans
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0082989
Abstract: A large body of evidence from human and animal studies demonstrates that the maternal diet during pregnancy can programme physiological and metabolic functions in the developing fetus, effectively determining susceptibility to later disease. The mechanistic basis of such programming is unclear but may involve resetting of epigenetic marks and fetal gene expression. The aim of this study was to evaluate genome-wide DNA methylation and gene expression in the livers of newborn rats exposed to maternal protein restriction. On day one postnatally, there were 618 differentially expressed genes and 1183 differentially methylated regions (FDR 5%). The functional analysis of differentially expressed genes indicated a significant effect on DNA repair/cycle/maintenance functions and of lipid, amino acid metabolism and circadian functions. Enrichment for known biological functions was found to be associated with differentially methylated regions. Moreover, these epigenetically altered regions overlapped genetic loci associated with metabolic and cardiovascular diseases. Both expression changes and DNA methylation changes were largely reversed by supplementing the protein restricted diet with folic acid. Although the epigenetic and gene expression signatures appeared to underpin largely different biological processes, the gene expression profile of DNA methyl transferases was altered, providing a potential link between the two molecular signatures. The data showed that maternal protein restriction is associated with widespread differential gene expression and DNA methylation across the genome, and that folic acid is able to reset both molecular signatures.
Page 1 /230476
Display every page Item


Home
Copyright © 2008-2017 Open Access Library. All rights reserved.