Coenzyme A restriction as a factor underlying pre-eclampsia and other antenatal conditions.

2021 ◽  
Author(s):  
Charlie Hodgman ◽  
William Atiomo ◽  
Gulafshana Khan
Keyword(s):  
Coenzyme A ◽  
Organ Damage ◽  
Feedback Loops ◽  
Regulatory Mechanisms ◽  
Profile Data ◽  
Metabolic Network Analysis ◽  
Sphingosine 1 Phosphate ◽  
Data Points ◽  
Gene Expression Profile Data ◽  
And Oxidative Stress

Abstract Pre-eclampsia is the most common pregnancy complication affecting 1 in 20 pregnancies, characterized by high blood pressure and signs of organ damage, most often to the liver and kidneys. Metabolic network analysis of published lipidomic data points to a shortage of Coenzyme A (CoA). Gene-expression profile data reveal alterations to many areas of metabolism and, crucially, to conflicting cellular regulatory mechanisms arising from the overproduction of signalling lipids driven by CoA limitation. Adverse feedback loops appear, forming sphingosine-1-phosphate (a cause of hypertension, hypoxia and inflammation), cytotoxic isoketovaleric acid (inducing acidosis and organ damage) and a thrombogenic lysophosphatidyl serine. These also induce mitochondrial and oxidative stress, leading to untimely apoptosis, which is possibly the cause of CoA restriction. This work provides a molecular basis for the signs of pre-eclampsia, why other conditions are risk factors and what might be done to treat and reduce the risk of this and related diseases.

scholarly journals Recurrent insulin-induced hypoglycemia induces AngII and COX2 leading to renal (pro)renin receptor expression and oxidative stress

2017 ◽  
Vol 5 (1) ◽  
pp. 71 ◽  
Author(s):  
Wael Alanazi ◽  
Mohammad Uddin ◽  
Selim Fakhruddin ◽  
Keith Jackson
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Kidney Injury ◽  
Organ Damage ◽  
Day Surgery ◽  
Receptor Expression ◽  
Sprague Dawley ◽  
Subunit Expression ◽  
Renal Biomarker ◽  
And Oxidative Stress

Background: Recurrent insulin-induced hypoglycemia (RIIH) is an avoidable consequence in the therapeutic management of diabetes mellitus. RIIH has been implicated in causing hypertension through an increase in renal and systemic AngII production.Objective: The present study was performed to assess the hypothesis that chronic insulin treatment enhances AngII and COX2 formation which in turn increases (pro) renin receptor (PRR) expression and NADPH oxidase-mediated oxidative stress, leading to renal and cardiac injury.Methods: The present studies were conducted in Male Sprague Dawley rats treated with daily subcutaneous injections of 7u/kg insulin or saline for 14 days. On the 14th day, surgery was performed for treatment infusion (captopril 12mg/kg, NS398 0.3mg/kg or vehicle), and renal interstitial fluid sample and urine collections for biomarker measurements. At the end of the experiments, kidneys and hearts were harvested to evaluate PRR and NOX2 (NADPH oxidase subunit) expression and oxidative stress.Results: We found that RIIH enhanced AngII and COX2 activity, leading to renal PRR expression and NADPH oxidase-induced oxidative stress in the heart and kidney. 8-isoprostane was evaluated as a renal biomarker of oxidative stress, which was induced in insulin treated animals and modulated by captopril and NS398. In addition, there was a slight increase in NGAL, a urinary biomarker of acute kidney injury (AKI), in insulin treated animals when compared to control.Conclusion: These results demonstrate that RIIH induces renal PRR expression and oxidative stress through increasing AngII and COX2 in the heart and kidney, leading to end-organ damage.

scholarly journals Transcriptome Analysis Reveals IsiA-Regulatory Mechanisms Underlying Iron Depletion and Oxidative-Stress Acclimation in Synechocystis sp. Strain PCC 6803

2020 ◽  
Vol 86 (13) ◽  
Author(s):  
Yarui Cheng ◽  
Tianyuan Zhang ◽  
Li Wang ◽  
Wenli Chen
Keyword(s):  
Oxidative Stress ◽  
Network Analysis ◽  
Iron Deficiency ◽  
Regulatory Mechanisms ◽  
Functional Modules ◽  
Iron Stress ◽  
Iron Starvation ◽  
Stress Acclimation ◽  
And Oxidative Stress ◽  
Coexpression Network Analysis

ABSTRACT Microorganisms in nature are commonly exposed to various stresses in parallel. The isiA gene encodes an iron stress-induced chlorophyll-binding protein which is significantly induced under iron starvation and oxidative stress. Acclimation of oxidative stress and iron deficiency was investigated using a regulatory mutant of the Synechocystis sp. strain PCC 6803. In this study, the ΔisiA mutant grew more slowly in oxidative-stress and iron depletion conditions compared to the wild-type (WT) counterpart under the same conditions. Thus, we performed transcriptome sequencing (RNA-seq) analysis of the WT strain and the ΔisiA mutant under double-stress conditions to obtain a comprehensive view of isiA-regulated genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed significant differences between the WT strain and ΔisiA mutant, mainly related to photosynthesis and the iron-sulfur cluster. The deletion of isiA affects the expression of various genes that are involved in cellular processes and structures, such as photosynthesis, phycobilisome, and the proton-transporting ATPase complex. Weighted gene coexpression network analysis (WGCNA) demonstrated three functional modules in which the turquoise module was negatively correlated with superoxide dismutase (SOD) activity. Coexpression network analysis identified several hub genes of each module. Cotranscriptional PCR and reads coverage using the Integrative Genomics Viewer demonstrated that isiA, isiB, isiC, ssl0461, and dfp belonged to the isi operon. Three sRNAs related to oxidative stress were identified. This study enriches our knowledge of IsiA-regulatory mechanisms under iron deficiency and oxidative stress. IMPORTANCE This study analyzed the impact of isiA deletion on the transcriptomic profile of Synechocystis. The isiA gene encodes an iron stress-induced chlorophyll-binding protein, which is significantly induced under iron starvation. The deletion of isiA affects the expression of various genes that are involved in photosynthesis and ABC transporters. WGCNA revealed three functional modules in which the blue module was correlated with oxidative stress. We further demonstrated that the isi operon contained the following five genes: isiA, isiB, isiC, ssl0461, and dfp by cotranscriptional PCR. Three sRNAs were identified that were related to oxidative stress. This study enhances our knowledge of IsiA-regulatory mechanisms under iron deficiency and oxidative stress.

scholarly journals Gene expression profile data of the developing small intestine of Id2-deficient mice

Data in Brief ◽  
2019 ◽  
Vol 24 ◽  
pp. 103717
Author(s):  
Kentaro Mori ◽  
Kota Tamada ◽  
Hisanori Kurooka ◽  
Makoto Matsui ◽  
Toru Takumi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Small Intestine ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Profile Data ◽  
Gene Expression Profile Data ◽  
Deficient Mice

scholarly journals Regulatory mechanisms for liver acetyl-coenzyme A carboxylase

1972 ◽  
Vol 128 (1) ◽  
pp. 2P-2P ◽  
Author(s):  
S Numa ◽  
T Hashimoto ◽  
S Nakanishi
Keyword(s):  
Coenzyme A ◽  
Regulatory Mechanisms ◽  
Acetyl Coenzyme A ◽  
Acetyl Coenzyme ◽  
Acetyl Coenzyme A Carboxylase

Optimal Linear Fitting for Objective Determination of Ocean Mixed Layer Depth from Glider Profiles

2010 ◽  
Vol 27 (11) ◽  
pp. 1893-1898 ◽  
Author(s):  
Peter C. Chu ◽  
Chenwu Fan
Keyword(s):  
Mixed Layer ◽  
North Atlantic Ocean ◽  
Mixed Layer Depth ◽  
Maximum Error ◽  
Profile Data ◽  
Layer Depth ◽  
Linear Fitting ◽  
Error Ratio ◽  
Optimal Linear ◽  
Data Points

Abstract A new optimal linear fitting method has been developed to determine mixed layer depth from profile data. This methodology includes three steps: 1) fitting the profile data from the first point near the surface to a depth using a linear polynomial, 2) computing the error ratio of absolute bias of few data points below that depth versus the root-mean-square error of data points from the surface to that depth between observed and fitted data, and 3) finding the depth (i.e., the mixed layer depth) with maximum error ratio. Temperature profiles in the western North Atlantic Ocean over 14 November–5 December 2007, collected from two gliders (Seagliders) deployed by the Naval Oceanographic Office, are used to demonstrate the capability of this method. The mean quality index (1.0 for perfect determination) for determining mixed layer depth is greater than 0.97, which is much higher than the critical value of 0.8 for well-defined mixed layer depth with that index.

scholarly journals Comparative Effects of Phosphoenolpyruvate, a Glycolytic Intermediate, as an Organ Preservation Agent with Glucose and N-Acetylcysteine against Organ Damage during Cold Storage of Mouse Liver and Kidney

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Yoichi Ishitsuka ◽  
Yusuke Fukumoto ◽  
Yuki Kondo ◽  
Mitsuru Irikura ◽  
Daisuke Kadowaki ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Organ Preservation ◽  
Mouse Liver ◽  
Organ Damage ◽  
Histological Changes ◽  
Glycolytic Intermediate ◽  
Cold Preservation ◽  
Oxidative Stress Parameters ◽  
Liver And Kidney ◽  
And Oxidative Stress

We evaluated the usefulness of phosphoenolpyruvate (PEP), a glycolytic intermediate with antioxidative and energy supplementation potentials, as an organ preservation agent. Using ex vivo mouse liver and kidney of a static cold storage model, we compared the effects of PEP against organ damage and oxidative stress during cold preservation with those of glucose or N-acetylcysteine (NAC). Lactate dehydrogenase (LDH) leakage, histological changes, and oxidative stress parameters (measured as thiobarbituric acid reactive substance and glutathione content) were determined. PEP (100 mM) significantly prevented an increase in LDH leakage, histological changes, such as tubulonecrosis and vacuolization, and changes in oxidative stress parameters during 72 h of cold preservation in mouse liver. Although glucose (100 mM) partly prevented LDH leakage and histological changes, no effects against oxidative stress were observed. By contrast, NAC inhibited oxidative stress in the liver and did not prevent LDH leakage or histological changes. PEP also significantly prevented kidney damage during cold preservation in a dose-dependent manner, and the protective effects were superior to those of glucose and NAC. We suggest that PEP, a functional carbohydrate with organ protective and antioxidative activities, may be useful as an organ preservation agent in clinical transplantation.

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