TY - JOUR AU - Zahorán, S. AU - Szántó, P.R. AU - Bódi, Nikolett AU - Bagyánszki, Mária AU - Maléth, József AU - Hegyi, Péter AU - Sári, T. AU - Hermesz, Edit TI - Sustained maternal smoking triggers endothelial-mediated oxidative stress in the umbilical cord vessels, resulting in vascular dysfunction JF - ANTIOXIDANTS J2 - ANTIOXIDANTS-BASEL VL - 10 PY - 2021 IS - 4 PG - 15 SN - 2076-3921 DO - 10.3390/antiox10040583 UR - https://m2.mtmt.hu/api/publication/31969947 ID - 31969947 AB - Nitric oxide (NO) bioavailability is fundamental in the regulation of redox balance and functionality of the endothelium, especially in the case of the umbilical cord (UC), which has no innervation. The analysis of UC vessel-related complications could serve as a useful tool in the understanding of the pathophysiological mechanisms leading to neonatal cardiovascular disorders. Therefore, the aim of this study was to characterize the mechanisms that rule the severity of prenatal endothelial dysfunction, induced by the long-term effect of maternal smoking. Our analysis describes the initiation and the consequences of endothelial nitric oxide synthase (NOS3) deactivation, along with the up-regulation of possible compensatory pathways, using structural, molecular and biochemical approaches. This study was carried out on both the UC arteries and veins originated from neonates born to non-smoking and heavy-smoking mothers. The alterations stimulated by maternal smoking are vessel-specific and proportional to the level of exposure to harmful materials passed through the placenta. Typically, in the primarily exposed veins, an increased formation of reactive oxygen species and an up-regulation of the highly-efficient NOS2-NO producing pathway were detected. Despite all the extensive structural and functional damages, the ex vivo heat and cadmium ion-treated UC vein pieces still support the potential for stress response. LA - English DB - MTMT ER - TY - JOUR AU - Chakraborty, Payal AU - Dugmonits, Krisztina Nikoletta AU - Orvos, Hajnalka AU - Hermesz, Edit TI - Mature Twin Neonates Exhibit Oxidative Stress via Nitric Oxide Synthase Dysfunctionality. A Prognostic Stress Marker in the Red Blood Cells and Umbilical Cord Vessels TS - A Prognostic Stress Marker in the Red Blood Cells and Umbilical Cord Vessels JF - ANTIOXIDANTS J2 - ANTIOXIDANTS-BASEL VL - 9 PY - 2020 IS - 9 PG - 12 SN - 2076-3921 DO - 10.3390/antiox9090845 UR - https://m2.mtmt.hu/api/publication/31646685 ID - 31646685 LA - English DB - MTMT ER - TY - JOUR AU - Chakraborty, Payal AU - Dugmonits, Krisztina Nikoletta AU - Végh, Attila Gergely AU - Hollandi, Réka AU - Horváth, Péter AU - Maléth, József AU - Hegyi, Péter AU - Németh, Gábor AU - Hermesz, Edit TI - Failure in the compensatory mechanism in red blood cells due to sustained smoking during pregnancy JF - CHEMICO-BIOLOGICAL INTERACTIONS J2 - CHEM-BIOL INTERACT VL - 313 PY - 2019 PG - 7 SN - 0009-2797 DO - 10.1016/j.cbi.2019.108821 UR - https://m2.mtmt.hu/api/publication/30805026 ID - 30805026 N1 - Megosztott első szerzőség AB - Decrease in the bioavailability of vasoactive nitric oxide (NO), derived from the endothelial nitric oxide synthase (NOS3), underlines vascular endothelial damage. Our expanding knowledge on mature red blood cells (RBCs) makes it supposable that RBCs might contribute to vascular function and integrity via their active NO synthetizing system (RBC-NOS3). This "rescue" mechanism of RBCs could be especially important during pregnancy with smoking habit, when smoking acts as an additional stressor and causes active change in the redox status. In this study RBC populations of 82 non-smoking (RBC-NS) and 75 smoking (RBC-S) pregnant women were examined. Morphological variants were followed by confocal microscopy and quantified by a microscopy based intelligent analysis software. Fluorescence activated cell sorting was used to examine the translational and posttranslational regulation of RBC-NOS, Arginase-1 and the formation of the major product of lipid peroxidation, 4-hydroxy-2-nonenal. To survey the rheological parameters of RBCs like elasticity and plasticity atomic force microscopy-based measurement was applied. Significant morphological and functional differences of RBCs were found between the non-smoking and smoking groups. The phenotypic variations in RBC-S population, even the characteristic biconcave disc-shaped cells, could be connected to impaired NOS3 activation and are compromised in their physiological properties. Membrane lipid studies reveal an elevated lipid oxidation state well paralleled with the changed elastic and plastic activities. These features can form a basic tool in the prenatal health screening conditions; hence the compensatory mechanism of RBC-S population completely fails to sense and rescue the acute oxidative stress conditions. LA - English DB - MTMT ER - TY - JOUR AU - Dugmonits, Krisztina Nikoletta AU - Chakraborty, Payal AU - Hollandi, Réka AU - Zahorán, Szabolcs AU - Pankotai-Bodó, Gabriella AU - Horváth, Péter AU - Orvos, Hajnalka AU - Hermesz, Edit TI - Maternal Smoking Highly Affects the Function, Membrane Integrity, and Rheological Properties in Fetal Red Blood Cells JF - OXIDATIVE MEDICINE AND CELLULAR LONGEVITY J2 - OXID MED CELL LONGEV VL - 2019 PY - 2019 PG - 10 SN - 1942-0900 DO - 10.1155/2019/1509798 UR - https://m2.mtmt.hu/api/publication/30973749 ID - 30973749 N1 - Department of Biochemistry and Molecular Biology, Faculty of Science and Informatics, University of Szeged, Közép fasor 52, Szeged, H-6726, Hungary Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary Department of Pathology, Faculty of Medicine, University of Szeged, Szeged, Hungary Department of Obstetrics and Gynecology, Faculty of Medicine, University of Szeged, Szeged, Hungary Export Date: 17 February 2020 Correspondence Address: Hermesz, E.; Department of Biochemistry and Molecular Biology, Faculty of Science and Informatics, University of Szeged, Közép fasor 52, Hungary; email: hermesz@bio.u-szeged.hu AB - An understanding of the basic pathophysiological mechanisms of neonatal diseases necessitates detailed knowledge about the wide range of complications in the circulating fetal RBCs. Recent publications on adult red blood cells (RBCs) provide evidence that RBCs carry an active nitric oxide synthase (NOS3) enzyme and contribute to vascular functioning and integrity via their active nitric oxide synthesis. The aim of this study was to determine the effect of maternal smoking on the phenotypical appearance and functionality of fetal RBCs, based on morphological and molecular studies. We looked for possible links between vascular dysfunction and NOS3 expression and activation and its regulation by arginase (ARG1). Significant morphological and functional differences were found between fetal RBCs isolated from the arterial cord blood of neonates born to nonsmoking (RBC-NS,n=62) and heavy-smoking (RBC-S,n=51) mothers. Morphological variations were quantified by Advanced Cell Classifier, microscopy-based intelligent analysis software. To investigate the relevance of the newly suggested “erythrocrine” function in fetal RBCs, we measured the levels of NOS3 and its phosphorylation in parallel with the level of ARG1, as one of the major influencers of NOS3 dimerization, by fluorescence-activated cell sorting. Fetal RBCs, even the “healthy-looking” biconcave-shaped type, exhibited impaired NOS3 activation in the RBC-S population, which was paralleled with elevated ARG1 level, thus suggesting an increased redox burden. Our molecular data indicate that maternal smoking can exert marked effects on the circulating fetal RBCs, which could have a consequence on the outcome of in utero development. We hypothesize that any endothelial dysfunction altering NO production/bioavailability can be sensed by circulating fetal RBCs. Hence, we are putting forward the idea that neonatal RBC could serve as a real-time sensor for not only monitoring RBC-linked anomalies but also predicting the overall status of the vascular microenvironment. LA - English DB - MTMT ER - TY - JOUR AU - Zhou, Z AU - Mahdi, A AU - Tratsiakovich, Y AU - Zahorán, Szabolcs AU - Kovamees, O AU - Nordin, F AU - Uribe, Gonzalez AE AU - Alvarsson, M AU - Ostenson, CG AU - Andersson, DC AU - Hedin, U AU - Hermesz, Edit AU - Lundberg, JO AU - Yang, J AU - Pernow, J TI - Erythrocytes From Patients With Type 2 Diabetes Induce Endothelial Dysfunction Via Arginase I. JF - JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY J2 - J AM COLL CARDIOL VL - 72 PY - 2018 IS - 7 SP - 769 EP - 780 PG - 12 SN - 0735-1097 DO - 10.1016/j.jacc.2018.05.052 UR - https://m2.mtmt.hu/api/publication/3405409 ID - 3405409 N1 - Division of Cardiology, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden Department of Biochemistry and Molecular Biology, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden Division of Endocrinology and Diabetology, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden Heart and Vascular Theme, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden Division of Vascular Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden Cited By :130 Export Date: 3 March 2025 CODEN: JACCD Correspondence Address: Zhou, Z.; CMM L8:03, Sweden; email: zhichao.zhou@ki.se Chemicals/CAS: acetylsalicylic acid, 493-53-8, 50-78-2, 53663-74-4, 53664-49-6, 63781-77-1; arginase, 9000-96-8; insulin, 9004-10-8; metformin, 1115-70-4, 657-24-9; Arginase; arginase I, human; Enzyme Inhibitors; Reactive Oxygen Species; Vasodilator Agents Funding details: Diabetes Research and Wellness Foundation, DRWF Funding details: Hjärt-Lungfonden Funding details: Stockholms Läns Landsting Funding details: Vetenskapsrådet, VR Funding details: Novo Nordisk Fonden, NNF Funding text 1: Dr. Pernow has received grants to support this work from the Swedish Research Council, the Swedish Heart and Lung Foundation, the Stockholm County Council (ALF), the Karolinska Institutet/Stockholm County Council Strategic Cardiovascular Program, the Söderberg Foundation, the Novo Nordisk Foundation, and the Diabetes Research and Wellness Foundation. Dr. Zhou has received grants from the Olausson Fund of Thorax, Karolinska University Hospital and the Karolinska Institutet Fund for Young Scientist. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. AB - BACKGROUND: Cardiovascular complications are major clinical problems in type 2 diabetes mellitus (T2DM). The authors previously demonstrated a crucial role of red blood cells (RBCs) in control of cardiac function through arginase-dependent regulation of nitric oxide export from RBCs. There is alteration of RBC function, as well as an increase in arginase activity, in T2DM. OBJECTIVES: The authors hypothesized that RBCs from patients with T2DM induce endothelial dysfunction by up-regulation of arginase. METHODS: RBCs were isolated from patients with T2DM and age-matched healthy subjects and were incubated with rat aortas or human internal mammary arteries from nondiabetic patients for vascular reactivity and biochemical studies. RESULTS: Arginase activity and arginase I protein expression were elevated in RBCs from patients with T2DM (T2DM RBCs) through an effect induced by reactive oxygen species (ROS). Co-incubation of arterial segments with T2DM RBCs, but not RBCs from age-matched healthy subjects, significantly impaired endothelial function but not smooth muscle cell function in both healthy rat aortas and human internal mammary arteries. Endothelial dysfunction induced by T2DM RBCs was prevented by inhibition of arginase and ROS both at the RBC and vascular levels. T2DM RBCs induced increased vascular arginase I expression and activity through an ROS-dependent mechanism. CONCLUSIONS: This study demonstrates a novel mechanism behind endothelial dysfunction in T2DM that is induced by RBC arginase I and ROS. Targeting arginase I in RBCs may serve as a novel therapeutic tool for the treatment of endothelial dysfunction in T2DM. LA - English DB - MTMT ER - TY - JOUR AU - Dugmonits, Krisztina Nikoletta AU - Ferencz, Ágnes AU - Zahorán, Szabolcs AU - Juhász, Renáta AU - Talapka, Petra AU - Orvos, Hajnalka AU - Hermesz, Edit TI - Elevated levels of macromolecular damage are correlated with increased nitric oxide synthase expression in erythrocytes isolated from twin neonates JF - BRITISH JOURNAL OF HAEMATOLOGY J2 - BRIT J HAEMATOL VL - 174 PY - 2016 IS - 6 SP - 932 EP - 941 PG - 10 SN - 0007-1048 DO - 10.1111/bjh.14156 UR - https://m2.mtmt.hu/api/publication/3081914 ID - 3081914 AB - Pregnancy is a state associated with an enhanced metabolism and demand for O2 , which may lead to the overproduction of reactive oxygen species (ROS) and hence to oxidative stress. An elevated ROS level may result in delayed development and a low birth weight. The aim of this study was to reveal the consequences of multiple pregnancies on the redox status of neonatal human red blood cells (RBCs) and evaluate the role of endothelial nitric oxide synthase (NOS3) - expressing RBCs in the generation of oxidative stress. The study presents evidence of higher levels of production of hydrogen peroxide, peroxynitrite and nitrate content in the RBCs of twin neonates, clearly reflected by an elevated level of protein and lipid damages. This phenotype appears to be a consequence of multiple pregnancies, regardless of the level of maturity or the birth weight of the twins. Besides the higher level of ROS, there was a general decrease in the expression of genes coding for antioxidants. The first data are presented on NOS3-expressing neonatal human RBCs. The number of RBCs producing NOS3 was more than twice as high in twin neonates compared to singletons, with no correlation to maturity. LA - English DB - MTMT ER -