scholarly journals S-nitrosoglutathione reductase deficiency causes aberrant placental S-nitrosylation and preeclampsia

2020 ◽  
Author(s):  
Shathiyah Kulandavelu ◽  
Raul A Dulce ◽  
Christopher I Murray ◽  
Michael A Bellio ◽  
Julia Fritsch ◽  
...  
Keyword(s):  
Nitrosative Stress ◽  
Protein S ◽  
Fetal Mortality ◽  
Oxygen Species ◽  
Fetal Growth Retardation ◽  
Amino Acid Residues ◽  
Mortality And Morbidity ◽  
Therapeutic Implications ◽  
Concentric Hypertrophy ◽  
The Difference

ABSTRACTPreeclampsia (PE), a leading cause of maternal and fetal mortality and morbidity, is characterized by an increase in S-nitrosylated (SNO) proteins and reactive oxygen species (ROS), suggesting a pathophysiologic role for dysregulation in nitrosylation and nitrosative stress. Here we show that mice lacking S-nitrosoglutathione reductase (GSNOR−/−), a denitrosylase regulating protein S-nitrosylation, exhibit a PE phenotype, including hypertension, proteinuria, renal pathology, cardiac concentric hypertrophy, decreased placental vascularization, and fetal growth retardation. ROS, nitric oxide (NO) and peroxynitrite levels are elevated. Importantly, mass spectrometry reveals elevated placental SNO-amino acid residues in GSNOR−/−mice. Ascorbate reverses the phenotype except for fetal weight, reduces the difference in the S-nitrosoproteome, and identifies a unique set of SNO-proteins in GSNOR−/−mice. Importantly, the human preeclamptic placenta exhibits decreased GSNOR activity and increased nitrosative stress. Therefore, deficiency of GSNOR creates dysregulation of placental S-nitrosylation and preeclampsia in mice, which can be rescued by ascorbate. Coupled with similar findings in human placentas, these findings offer valuable insights and therapeutic implications for PE.

Abstract 66: Ascorbate Prevents Hypertension, Proteinuria and Concentric Hypertrophy by Balancing the Nitroso-redox System in a Model of Preeclampsia, the S-nitrosoglutathione Reductase (gsnor) Deficient Mice

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Shathiyah Kulandavelu ◽  
Raul A Dulce ◽  
Rosemeire K Takeuchi ◽  
Wayne Balkan ◽  
Joshua M Hare
Keyword(s):  
Nitrosative Stress ◽  
Fluorescent Dyes ◽  
Protein S ◽  
Redox System ◽  
Fetal Mortality ◽  
Mortality And Morbidity ◽  
Redox Imbalance ◽  
Concentric Hypertrophy ◽  
Maternal Hypertension ◽  
And Control

Introduction: Preeclampsia (PE), a leading cause of maternal and fetal mortality and morbidity, is characterized by increased levels of reactive oxygen species (ROS) and S-nitrosylated protein, and decreased levels of the antioxidant, ascorbate (Asc). Mice lacking S-nitrosoglutathione reductase (GSNOR –/– ), a denitrosylase that regulates protein S-nitrosylation, exhibit a PE-like phenotype including maternal hypertension, proteinuria, cardiac concentric hypertrophy and impaired placental vascularization. We hypothesize that the PE-like phenotype is mediated by nitroso-redox imbalance and nitrosative stress and can be rescued with ascorbate treatment. Methods: Pregnant GSNOR –/– and control (WT) mice (n=5-7) were provided drinking water ± Asc beginning at day 0.5 of gestation (E0.5). We determined blood pressure using a Millar catheter, relative wall thickness (RWT) by echocardiography, and placental vascularization by isolectin staining. Cardiomyocytes (CM) were isolated at late stage pregnancy (E17.5) and fluorescent dyes used to determine levels of ROS (2’7’-dichlorofluorescein), nitric oxide (NO, diaminofluorescin) and peroxynitrite (dihydrorhodamine 123). Results: Isolated CMs from pregnant GSNOR –/– hearts, exhibited elevated levels of ROS (2.48±0.39 vs. 1.58±0.18 ΔF/F 0 ), free NO (6.65±0.43 vs. 5.59±0.26 ΔF/F 0 ) and peroxynitrite (0.75±0.04 vs. 0.39±0.03 ΔF/F 0 ) compared to WT. These increases were prevented with Asc treatment (P<0.01), which completely rescued the PE phenotype in GSNOR –/– mothers, including hypertension (105±2 mmHg vs. 95± mmHg in Asc-treated, P<0.05), proteinuria (P<0.05) and RWT (0.56±0.04 vs. 0.45±0.03 in Asc-treated (P<0.05). Placental vascularization was also significantly improved with Asc treatment in GSNOR –/– mothers. Asc had no significant effect in WT mice. Conclusion: Our findings indicate that nitroso-redox imbalance and nitrosative stress contributes to PE in mice. Asc treatment balanced the nitroso-redox system and rescued the pathological phenotypes in GSNOR –/– mice, suggesting that it can be used therapeutically to treat or prevent preeclampsia.

Abstract 238: S-nitrosoglutathione Reductase (GSNOR) Plays a Critical Role in Placental Vascularization Working Through the VEGF-NO Pathway

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Shathiyah Kulandavelu ◽  
Michael A Bellio ◽  
Julia Fritsch ◽  
Wayne Balkan ◽  
Joshua M Hare
Keyword(s):  
Nitrosative Stress ◽  
Critical Role ◽  
Late Pregnancy ◽  
Protein S ◽  
Capillary Density ◽  
Fetal Mortality ◽  
Mortality And Morbidity ◽  
Working Through ◽  
Concentric Hypertrophy ◽  
Enos Protein

Introduction: Preeclampsia (PE), a leading cause of maternal and fetal mortality and morbidity, is characterized by increased levels of reactive oxygen species (ROS) and S-nitrosylated protein, and decreased levels of the antioxidant, ascorbate (Asc), which is required for the release of nitric oxide (NO) from nitrosylated proteins. Mice lacking S-nitrosoglutathione reductase (GSNOR –/– ), a denitrosylase that regulates protein S-nitrosylation, exhibit a PE-like phenotype including maternal hypertension, cardiac concentric hypertrophy and impaired placental vascularization. We hypothesized that impaired placental vascularization, one of the primary causes of preeclampsia is mediated by alteration in S-nitrosylation of the VEGF-NO pathway, and ascorbate treatment rescues this pathologic phenotype. Methods: Pregnant GSNOR –/– and control (WT) mice (n=5-7) were studied at late pregnancy (day 17.5). Ascorbate was provided in drinking water beginning at day 0.5. Fetoplacental capillary density was determined from isolectin staining and reactive nitrosative stress determined from nitrotyrosine staining in placental sections. S-nitrosylation of VEGF was determined using SNO-Rac and eNOS levels by Western blot analysis. Results: Fetoplacental capillary density was reduced 19% in GSNOR –/– fetuses compared to WT (P<0.001). GSNOR –/– placentas exhibited higher nitrotyrosine staining than WT placentas, indicating the presence of nitrosative stress. These increases were associated with reduced level of eNOS protein (P<0.05) and decreased S-nitrosylation of VEGF (P<0.05) in the GSNOR –/– placentas as compared to WT. Ascorbate treatment decreased nitrotyrosine staining, and increased fetoplacental capillary density ~10% (P<0.001), eNOS protein levels (P<0.05) and S-nitrosylation of VEGF (P<0.05) in the GSNOR –/– placentas as compared to WT. Conclusion: These findings suggest that GSNOR plays an essential role in promoting placental vascularization in part working through the VEGF-NO pathway. Ascorbate treatment rescued the nitrosative stress and improved placental vascularization, suggesting that it can be used therapeutically to treat or prevent preeclampsia.

scholarly journals MANAGEMEN KELELAHAN SAAT PERSALINAN MENGGUNAKAN JUS SEMANGKA

2018 ◽  
Vol 12 (1) ◽  
pp. 19
Author(s):  
Islah Wahyuni
Keyword(s):  
Post Partum ◽  
Fetal Mortality ◽  
Control Group ◽  
Normal Delivery ◽  
Mortality And Morbidity ◽  
Watermelon Juice ◽  
Before And After ◽  
The Difference ◽  
Lactate Levels ◽  
And Control

<em>The condition of fatigue during labor has received little attention for meditative intervention, so it is important in suppressing the adverse effects of fatigue during labor on the mother and fetus, and preventing the incidence of maternal and fetal mortality and morbidity. The purpose of the study to determine the handling of fatigue using watermelon juice in maternal mothers. Anaerobic fatigue was measured using blood lactic acid values, and Visual Analoque Scale-Fatique (VAS-F) quetioner from 68 respondents were divided into 2 groups: treatment and control group were selected concencutive sampling.  Measurement of blood lactate level was performed 2x at before and after treatment. Data analysis was using univariate and bivariate by dependent T test. The results showed that there were significant differences between lactate levels before and after treatment and control group (.003). The VAS-Fatique analysis resulted  the difference in fatigue experienced stage 1 (.015) and  fatigue experienced 24 hour post partum (.001) is lower treatment group compared with the control group. In conclusion, watermelon juice is effective as fatigue handling in maternal mothers, it is recommended that watermelon juice be given to the mother during normal delivery</em>

scholarly journals Subcellular localization and purification of a p-hydroxyphenylpyruvate dioxygenase from cultured carrot cells and characterization of the corresponding cDNA

1997 ◽  
Vol 325 (3) ◽  
pp. 761-769 ◽  
Author(s):  
Isabelle GARCIA ◽  
Matthew RODGERS ◽  
Catherine LENNE ◽  
Anne ROLLAND ◽  
Alain SAILLAND ◽  
...  
Keyword(s):  
Nucleotide Sequence ◽  
Gel Filtration ◽  
Peptide Sequence ◽  
Amino Acid Residues ◽  
Carrot Cells ◽  
Expression Studies ◽  
Sds Page ◽  
Molecular Masses ◽  
The Difference ◽  
Dioxygenase Activity

p-Hydroxyphenylpyruvate dioxygenase catalyses the transformation of p-hydroxyphenylpyruvate into homogentisate. In plants this enzyme has a crucial role because homogentisate is the aromatic precursor of all prenylquinones. Furthermore this enzyme was recently identified as the molecular target for new families of potent herbicides. In this study we examine precisely the localization of p-hydroxyphenylpyruvate dioxygenase activity within carrot cells. Our results provide evidence that, in cultured carrot cells, p-hydroxyphenylpyruvate dioxygenase is associated with the cytosol. Purification and SDS/PAGE analysis of this enzyme revealed that its activity is associated with a polypeptide of 45–46 kDa. This protein specifically cross-reacts with an antiserum raised against the p-hydroxyphenylpyruvate dioxygenase of Pseudomonas fluorescens. Gel-filtration chromatography indicates that the enzyme behaves as a homodimer. We also report the isolation and nucleotide sequence of a cDNA encoding a carrot p-hydroxyphenylpyruvate dioxygenase. The nucleotide sequence (1684 bp) encodes a protein of 442 amino acid residues with a molecular mass of 48094 Da and shows specific C-terminal regions of similarity with other p-hydroxyphenylpyruvate dioxygenases. This cDNA encodes a functional p-hydroxyphenylpyruvate dioxygenase, as evidenced by expression studies with transformed Escherichia coli cells. Comparison of the N-terminal sequence of the 45–46 kDa polypeptide purified from carrot cells with the deduced peptide sequence of the cDNA confirms that this polypeptide supports p-hydroxyphenylpyruvate dioxygenase activity. Immunodetection studies of the native enzyme in carrot cellular extracts reveal that N-terminal proteolysis occurs during the process of purification. This proteolysis explains the difference in molecular masses between the purified protein and the deduced polypeptide.

scholarly journals Evidence for Detrimental Cross Interactions between Reactive Oxygen and Nitrogen Species in Leber’s Hereditary Optic Neuropathy Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Micol Falabella ◽  
Elena Forte ◽  
Maria Chiara Magnifico ◽  
Paolo Santini ◽  
Marzia Arese ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Optic Neuropathy ◽  
Nitrosative Stress ◽  
Mononuclear Cells ◽  
Reactive Oxygen ◽  
Leber’S Hereditary Optic Neuropathy ◽  
Oxygen Species ◽  
Nitrogen Species ◽  
Leber's Hereditary Optic Neuropathy ◽  
Hereditary Optic Neuropathy

Here we have collected evidence suggesting that chronic changes in the NO homeostasis and the rise of reactive oxygen species bioavailability can contribute to cell dysfunction in Leber’s hereditary optic neuropathy (LHON) patients. We report that peripheral blood mononuclear cells (PBMCs), derived from a female LHON patient with bilateral reduced vision and carrying the pathogenic mutation 11778/ND4, display increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS), as revealed by flow cytometry, fluorometric measurements of nitrite/nitrate, and 3-nitrotyrosine immunodetection. Moreover, viability assays with the tetrazolium dye MTT showed that lymphoblasts from the same patient are more sensitive to prolonged NO exposure, leading to cell death. Taken together these findings suggest that oxidative and nitrosative stress cooperatively play an important role in driving LHON pathology when excess NO remains available over time in the cell environment.

scholarly journals Structural Analysis of Yoked Chorionic Gonadotropin-Luteinizing Hormone Receptor Ectodomain Complexes by Circular Dichroic Spectroscopy

2003 ◽  
Vol 17 (7) ◽  
pp. 1192-1202 ◽  
Author(s):  
Gregory B. Fralish ◽  
Brian Dattilo ◽  
David Puett
Keyword(s):  
Chorionic Gonadotropin ◽  
Fusion Proteins ◽  
Homology Model ◽  
Difference Spectrum ◽  
Luteinizing Hormone Receptor ◽  
Amino Acid Residues ◽  
Single Chain ◽  
Glycoprotein Hormone ◽  
The Difference ◽  
Α Helix

Abstract Binding of the heterodimeric glycoprotein hormone, chorionic gonadotropin (CG), occurs to the heptahelical LH receptor N-terminal ectodomain (ECD), a large portion of which has been modeled as a leucine-rich repeat protein. In this study, we expressed and purified three single chain N-CG-ECD-C complexes, one comprising the full-length ECD, 1–341 (encoded by exons 1–10 and a portion of 11), and two C-terminal ECD deletion fragments, 1–294 (encoded by exons 1–10) and 1–180 (encoded by exons 1–7). The fusion proteins, including yoked CG (N-β-α-C), were characterized by Western blot analysis and circular dichroism (CD). Analysis of the CD spectra obtained on the CG-ECD fusion proteins, and of the difference spectrum of each after subtracting the CG contribution, yielded secondary structures consistent with a repeating β-strand/α-helix fold as predicted in the homology model. A marked decrease in helicity was observed when the C-terminal 47 amino acid residues were removed from the ECD. Removal of an additional 114 residues, i.e. the region encoded by exons 8–10, results in the loss of fewer helical residues. These results suggest that the hinge region of the ECD, predicted to contain only limited secondary structure, interacts with and stabilizes the ligand-occupied N-terminal portion. Furthermore, the results support a repeating fold, consistent with the proposed model for the LHR ECD.

scholarly journals Perinatal Findings in Pregnancy Induced Hypertension: A Study in a Tertiary Teaching Hospital in Dhaka City

2017 ◽  
Vol 2 (1) ◽  
pp. 10-13
Author(s):  
Zobaida Sultana Susan ◽  
Surayea Bulbul ◽  
Jannat Ara Ferdows ◽  
Abu Nayeem
Keyword(s):  
Cross Sectional Study ◽  
Fetal Mortality ◽  
Pregnancy Induced Hypertension ◽  
College Hospital ◽  
Cross Sectional ◽  
Mortality And Morbidity ◽  
Tertiary Teaching ◽  
Induced Hypertension ◽  
Questionnaire Result ◽  
In Pregnancy

Background: Hypertensive disorders are common complication occurring during pregnancy which are responsible for maternal and fetal mortality and morbidity. Objective: The purpose of the present study was to determine the perinatal outcome in pregnancy induced hypertension. Methodology: This study was designed as cross-sectional study and was conducted from April 2013 to September 2013 for a period of six (06) moths. Patients admitted in the Department of Obstetrics and Gynaecology at Shaheed SuhrawardyMedical College Hospital, Dhaka. Data were collected by interview, physical examintions (blood pressure, pulse rate, oedema, heart and lungs auscultation) and lab investigations using a structural questionnaire. Result: Majority of the women belonged to age group 21-25 year. Maximum were (56%) primigravida. The mean gestational age was 34.6 weeks with the range from 28 to 40 weeks. Hyperurecaemia was frequent among patients with pregnancy induced hypertension. Intrauterine growth retardation (IUGR) was secondary to pregnancy induced hypertension which was associated with significantly increased perinatalmortality. Conclusion: In this study, prematurity is frequent in pregnancy induced hypertension and convulsion in nonresponsive patients is associated with significantly increased perinatal mortality.Journal of National Institute of Neurosciences Bangladesh, January 2016;2(1): 10-13

Influence of Blood Group and Secretor Status on Carbohydrate Structures in Human Gastric Mucins: Implications for Peptic Ulcer

1995 ◽  
Vol 89 (4) ◽  
pp. 405-415 ◽  
Author(s):  
R. L. Sidebotham ◽  
J. H. Baron ◽  
J. Schrager ◽  
J. Spencer ◽  
J. R. Clamp ◽  
...  
Keyword(s):  
Peptic Ulcer ◽  
Amino Acid ◽  
Blood Group ◽  
Average Length ◽  
Amino Acid Residues ◽  
Secretor Status ◽  
Increased Risk ◽  
The Mean ◽  
The Difference ◽  
Carbohydrate Chains

1. The content and distribution of carbohydrate was examined in mucus glycopolypeptides from human antral mucosae. 2. The mean amount of carbohydrate per 1000 amino acid residues was found to be similar in glycopolypeptides with A, B or H activity. It was slightly, though significantly, less in glycopolypeptides lacking these determinants, because carbohydrate chains were of a shorter average length than in the A-, B- or H-active preparations. This difference was reflected in the sizes of oligosaccharide—alcohols released from representative glycopolypeptides with alkaline borohydride. 3. Differences between A-, B- or H-active and non-secretor glycopolypeptides in terms of the mean number of carbohydrate chains per 1000 amino acid residues were found to be small, and without significance. 4. The average number of peripheral monosaccharide units per 1000 amino acid residues was greater in A-active than in H-active, and least in non-secretor, glycopolypeptides. This order was reversed for monosaccharide units incorporated into skeletal (core plus backbone) structures. The difference in each case was statistically significant. 5. These findings suggest that the increased risk of peptic ulcer associated with blood group O and non-secretor status is unlikely to be attributable to an inherent deficiency in the protective mucus layer, linked to differences between mucins that are associated with A, B or H activity. Other hypotheses linked to infection with Helicobacter pylori are examined.

scholarly journals Venous Thromboembolic Disease and Bone Marrow Transplant: A Remarkable Cause of Mortality and Morbidity — Potentially Preventable

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5070-5070
Author(s):  
Marta Rivas Luque ◽  
Estefanía Morente Constantin ◽  
Pablo Romero Garcia ◽  
Maria Almudena Garcia-Ruiz ◽  
Manuel Jurado
Keyword(s):  
Medical History ◽  
Conflicts Of Interest ◽  
Protein S ◽  
Marrow Transplant ◽  
Morbidity And Mortality ◽  
Hematopoietic Stem ◽  
Mortality And Morbidity ◽  
Vein Thrombosis ◽  
Venous Thromboembolic ◽  
Hemorrhagic Risk

Abstract Thrombotic events are frequent in patients undergoing HSCT, being an important cause of morbidity and mortality. The highest incidence occurs three months after the transplant. There are several risk factors, which add to those already known for VTE: neoplasia, central venous catheters, immobilization, chemotherapy, infections, GVHD. In the series described, the frequencies are variable, between 0.5 and 23.5%, with an overall incidence of 5%. In patients with GVHD, this incidence increases, with up to 35% of events. METHODS A retrospective observational study that includes patients transplanted in our Unit between 2014 and 2017 has been conducted, with the objective of analyzing the incidence of VTE peri-TPH. Likewise, we have analyzed if it is associated to catheter, presence of CVRF, if there was a known medical history of thrombophilia, number of platelets at time of thrombosis, the heparin used and whether anticoagulation was maintained indefinitely or not. RESULTS Out of the 235 patients included in our series, 130 underwent an autologous transplant and 105 an allogeneic transplant. 18 thrombotic events occurred (9 men and 9 women, aged between 18 and 65 years), which means 7.5% (14 occurred between days 0-100, 12 in patients undergoing autologous hematopoietic stem cell transplantation). Three of them had thromboembolism and the rest deep vein thrombosis, 4 of which with catheter. The platelet count at the time of the event ranges from 21 to 409,000 / mm3. Regarding the heparin used, 2 were treated with Tinzaparin and the rest with Bemiparin. Only 1 of the patients presented prior VTE. Among the patients, there were some with CVRF and others without relevant medical history. Just in one patient, a family thrombophilia study had been performed prior to his hematological diagnosis, resulting in a deficit of protein S. In 8 of the patients, anticoagulation was maintained indefinitely with LMWH in the post-transplant period. CONCLUSIONS Our incidence approaches the literature, albeit the series of published cases are heterogeneous and with variable differences. Although the incidence of thrombosis in these patients is a cause of marked morbidity and mortality, the risk of bleeding also increases, therefore routine prophylaxis is not recommended in all patients. We must undergo an exhaustive analysis of the data to identify individually which patients may be candidates for prophylaxis, with the aim of reducing the incidence without raising the hemorrhagic risk of our patients. Disclosures No relevant conflicts of interest to declare.

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