scholarly journals Oxidation of 5-methylaminomethyl uridine (mnm5U) by Oxone Leads to Aldonitrone Derivatives

Biomolecules ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 145 ◽  
Author(s):  
Qishun Zhou ◽  
Bao Vu Ngoc ◽  
Grazyna Leszczynska ◽  
Jean-Luc Stigliani ◽  
Geneviève Pratviel
Keyword(s):  
Oxidation Products ◽  
Cell Dysfunction ◽  
Rna Damage ◽  
Aldehyde Derivative

Oxidative RNA damage is linked to cell dysfunction and diseases. The present work focuses on the in vitro oxidation of 5-methylaminomethyl uridine (mnm5U), which belongs to the numerous post-transcriptional modifications that are found in tRNA. The reaction of oxone with mnm5U in water at pH 7.5 leads to two aldonitrone derivatives. They form by two oxidation steps and one dehydration step. Therefore, the potential oxidation products of mnm5U in vivo may not be only aldonitrones, but also hydroxylamine and imine derivatives (which may be chemically more reactive). Irradiation of aldonitrone leads to unstable oxaziridine derivatives that are susceptible to isomerization to amide or to hydrolysis to aldehyde derivative.

scholarly journals Suppression of Peroxisome Proliferator-Activated Receptor γ-Coactivator-1α Normalizes the Glucolipotoxicity-Induced Decreased BETA2/NeuroD Gene Transcription and Improved Glucose Tolerance in Diabetic Rats

Endocrinology ◽  
2009 ◽  
Vol 150 (9) ◽  
pp. 4074-4083 ◽  
Author(s):  
Ji-Won Kim ◽  
Young-Hye You ◽  
Dong-Sik Ham ◽  
Jae-Hyoung Cho ◽  
Seung-Hyun Ko ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Receptor Site ◽  
Diabetic Rats ◽  
Peroxisome Proliferator ◽  
Β Cells ◽  
Β Cell ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cell Dysfunction

Abstract Peroxisome proliferator-activated receptor γ-coactivator-1α (PGC-1α) is significantly elevated in the islets of animal models of diabetes. However, the molecular mechanism has not been clarified. We investigated whether the suppression of PGC-1α expression protects against β-cell dysfunction in vivo and determined the mechanism of action of PGC-1α in β-cells. The studies were performed in glucolipotixicity-induced primary rat islets and INS-1 cells. In vitro and in vivo approaches using adenoviruses were used to evaluate the role of PGC-1α in glucolipotoxicity-associated β-cell dysfunction. The expression of PGC-1α in cultured β-cells increased gradually with glucolipotoxicity. The overexpression of PGC-1α also suppressed the expression of the insulin and β-cell E-box transcription factor (BETA2/NeuroD) genes, which was reversed by PGC-1α small interfering RNA (siRNA). BETA2/NeuroD, p300-enhanced BETA2/NeuroD, and insulin transcriptional activities were significantly suppressed by Ad-PGC-1α but were rescued by Ad-siPGC-1α. PGC-1α binding at the glucocorticoid receptor site on the BETA2/NeuroD promoter increased in the presence of PGC-1α. Ad-siPGC-1α injection through the celiac arteries of 90% pancreatectomized diabetic rats improved their glucose tolerance and maintained their fasting insulin levels. The suppression of PGC-1α expression protects the glucolipotoxicity-induced β-cell dysfunction in vivo and in vitro. A better understanding of the functions of molecules such as PGC-1α, which play key roles in intracellular fuel regulation, could herald a new era of the treatment of patients with type 2 diabetes mellitus by providing protection from glucolipotoxicity, which is an important cause of the development and progression of the disease.

Abstract 064: The Lipoxigenase Inhibitor Nordihydroguaiaretic Acid Prevents the Development of Hypoxia-Induced Pulmonary Hypertension in Mice

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Andrea Iorga ◽  
Gabriel Wong ◽  
Denise Mai ◽  
Jingyuan Li ◽  
Salil Sharma ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Smooth Muscle ◽  
Smooth Muscle Actin ◽  
Nordihydroguaiaretic Acid ◽  
Treated Group ◽  
Oxidation Products ◽  
Lipoxygenase Inhibitor ◽  
Human Pulmonary Artery

Pulmonary hypertension (PH) is a chronic lung disease characterized by progressively elevated pulmonary arterial pressures and severe pulmonary vascular remodeling resulting from interactions between oxidized lipoprotein deposition and increased endothelial proliferation. Previously we have shown increased plasma levels of biological oxidation products such as hydroxyoctadecadienoic acids (HODEs) and hydroxyeicosatetraenoic acids (HETEs) in the rat monocrotaline model of PH. Here we investigated the role of HETEs and HODEs in the development of PH and whether their inhibition with the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) attenuates the progression of PH. Mice were placed in a hypoxic chamber with O2 concentrations of ≤10% for 21 days and either left untreated to develop PH (n=7) or treated with NDGA daily (10mg/kg/day, i.p., n=4) from day 1. Direct RV catheterization was terminally performed to record RV pressure (RVP). Pulmonary arteriolar thickening and oxidized lipid deposition were assessed by staining lung sections with Masson’s Trichrome or with α-smooth muscle actin and E-06 (marker for oxidized low-density lipoproteins). In vitro, human pulmonary artery smooth muscle cell (hPASMC) proliferation was assessed by MTT assays in the absence or presence of 12-HETE (100ng/ml), 9-HODE (1µg/ml) and 13-HODE (1µg/ml) alone or together with NDGA (10, 25 and 50µM). In-vitro, HETE/HODE treatment increased hPASMC proliferation ~ 2-fold when compared to untreated cells and NDGA significantly inhibited the proliferative effects of all three oxidized lipids. In-vivo, NDGA treatment prevented the development of PH. RVP was lower in the NDGA-treated group vs. the PH group (24.01±1.39mmHg vs. 36.91±5.74mmHg, p<0.05) and was comparable to control normoxic mice (20.93±2.52mmHg). RV hypertrophy index was significantly elevated in the PH mice versus control mice (0.38±0.03 vs. 0.28±0.02 (p<0.001), while NDGA treatment completely prevented the development of RV hypertrophy (0.28±0.04). Lung sections demonstrated arteriolar thickening and E-06 positive deposits in the PH group, which was prevented by NDGA therapy. We conclude that oxidized fatty acid deposition and accumulation might play a role in the development of PH.

scholarly journals Formation of electrophilic oxidation products from mitochondrial cardiolipin in vitro and in vivo in the context of apoptosis and atherosclerosis

Redox Biology ◽  
2014 ◽  
Vol 2 ◽  
pp. 878-883 ◽  
Author(s):  
Huiqin Zhong ◽  
Jianhong Lu ◽  
Lin Xia ◽  
Mingjiang Zhu ◽  
Huiyong Yin
Keyword(s):  
Oxidation Products

scholarly journals Escaping High Viral Load Exhaustion

2002 ◽  
Vol 195 (9) ◽  
pp. 1089-1101 ◽  
Author(s):  
Stephanie Reignat ◽  
George J.M. Webster ◽  
David Brown ◽  
Graham S. Ogg ◽  
Abigail King ◽  
...  
Keyword(s):  
Viral Infections ◽  
Low Frequency ◽  
High Viral Load ◽  
Functional Impairments ◽  
Cd8 Cells ◽  
Cell Dysfunction ◽  
Chronic Hepatitis B Virus ◽  
The Face

Deletion, anergy, and a spectrum of functional impairments can affect virus-specific CD8 cells in chronic viral infections. Here we characterize a low frequency population of CD8 cells present in chronic hepatitis B virus (HBV) infection which survive in the face of a high quantity of viral antigen. Although they do not appear to exert immunological pressure in vivo, these CD8 cells are not classically “tolerant” since they proliferate, lyse, and produce antiviral cytokines in vitro. They are characterized by altered HLA/peptide tetramer reactivity, which is not explained by TCR down-regulation or reduced functional avidity and which can be reversed with repetitive stimulation. CD8 cells with altered tetramer binding appear to have a specificity restricted to envelope antigen and not to other HBV antigens, suggesting that mechanisms of CD8 cell dysfunction are differentially regulated according to the antigenic form and presentation of individual viral antigens.

scholarly journals Oxidation of Bilirubin Produces Compounds that Cause Prolonged Vasospasm of Rat Cerebral Vessels: A Contributor to Subarachnoid Hemorrhage–Induced Vasospasm

2002 ◽  
Vol 22 (4) ◽  
pp. 472-478 ◽  
Author(s):  
Joseph F. Clark ◽  
Melinda Reilly ◽  
Frank R. Sharp
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Stress Protein ◽  
Cerebral Vessels ◽  
Oxidation Products ◽  
Adult Rats ◽  
Cranial Window ◽  
Related Stress ◽  
Protein Response

The authors have previously shown that bilirubin-oxidation products (BOXes) are present in CSF of subarachnoid hemorrhage patients with vasospasm, and that BOXes cause vasoconstriction in vitro. This study determined whether BOXes cause vasospasm in vivo. Identical volumes of either lysed blood or standardized amounts of BOXes were injected into the cisterna magna of adult rats. BOX injections caused 6 of 10 rats to die within 10 minutes, whereas 12 of 12 rats survived for 24 hours after blood injections. The mechanism for this significant ( P ⩽ 0.01) increase in mortality was unclear. To directly test whether BOXes produced vasospasm, a cranial window technique was used. Application of 20 μL of 10-μmol/L bilirubin had little effect on the vessels. However, application of BOXes produced marked, dose-dependent small artery and arteriole vasospasm that approached a 90% decrease in diameter by 40 minutes after application in some vessels, and persisted for at least 24 hours. To determine if BOX-mediated vasospasm led to cortical injury, histology and immunocytochemistry were performed on animals that survived for 24 hours. There was a BOX-related stress protein response for HSP25 and HSP32 (HO-1) without evidence of infarction. The finding that the BOXes produce vasospasm of cerebral vessels in vivo, in conjunction with BOXes being found in CSF of vasospasm patients, supports our hypothesis that BOXes contribute to or cause cerebral vasospasm after subarachnoid hemorrhage.

Calcium-translocating and cardiotonic properties of oxidation products of linoleic acid

1985 ◽  
Vol 63 (11) ◽  
pp. 1392-1397 ◽  
Author(s):  
Ryungsoon Song Kim ◽  
Ivan Bihler ◽  
Frank S. LaBella
Keyword(s):  
Linoleic Acid ◽  
Calcium Ionophore ◽  
Physiological Role ◽  
Calcium Ionophore A23187 ◽  
Oxidation Products ◽  
Ionophore A23187 ◽  
Guinea Pig Heart ◽  
Adrenergic Antagonist

Calcium-translocating activity of linoleic acid and its lipoxygenase (linoleate: oxygen oxidoreductase; EC 1.13.11.12) metabolites or autoxidation products was determined in vitro by estimation of 45Ca transport from a bulk aqueous to a bulk organic phase. Fresh commercial linoleic acid, tested immediately after removal from a sealed vial, stimulated calcium translocation only at concentrations greater than 1 mM. In contrast, 45Ca translocation by linoleic acid exposed to air was detectable at 10 μM. Oxidation products of linoleic acid obtained either by incubation with lipoxygenase or by autoxidation were much less potent than the calcium ionophore A23187. The products obtained by enzymic oxidation of linoleic acid enhanced contractility in the Langendorff-perfused guinea pig heart up to 45% over control (at 3 × 10−8 M). The inotropic response was transient with rapid onset and not affected by the beta-adrenergic antagonist, propranolol. The autoxidation products of linoleic acid increased cardiac contractility up to 43% at 10−6 M. In contrast, fresh linoleic acid caused only a negative inotropic effect at 10−8 to 3 × 10−7 M, progressing to contracture at 10−6 M. These findings suggest that conflicting reports on the cardiostimulant effect of linoleic acid may be due to varying levels of the autoxidation products. Linoleic acid metabolites in vivo may have a physiological role in myocardial function related to their Ca2+-ionophoric activity.

scholarly journals The Attenuation of Moutan Cortex on Oxidative Stress for Renal Injury in AGEs-Induced Mesangial Cell Dysfunction and Streptozotocin-Induced Diabetic Nephropathy Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Minghua Zhang ◽  
Liang Feng ◽  
Junfei Gu ◽  
Liang Ma ◽  
Dong Qin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Transforming Growth Factor Beta ◽  
High Glucose ◽  
Transforming Growth Factor ◽  
Mesangial Cell ◽  
Cell Dysfunction ◽  
Moutan Cortex

Oxidative stress (OS) has been regarded as one of the major pathogeneses of diabetic nephropathy (DN) through damaging kidney which is associated with renal cells dysfunction. The aim of this study was to investigate whether Moutan Cortex (MC) could protect kidney function against oxidative stressin vitroorin vivo. The compounds in MC extract were analyzed by HPLC-ESI-MS. High-glucose-fat diet and STZ (30 mg kg−1) were used to induce DN rats model, while 200 μg mL−1AGEs were for HBZY-1 mesangial cell damage. The treatment with MC could significantly increase the activity of SOD, glutathione peroxidase (GSH-PX), and catalase (CAT). However, lipid peroxidation malondialdehyde (MDA) was reduced markedlyin vitroorin vivo. Furthermore, MC decreased markedly the levels of blood glucose, serum creatinine, and urine protein in DN rats. Immunohistochemical assay showed that MC downregulated significantly transforming growth factor beta 2 (TGF-β2) protein expression in renal tissue. Our data provided evidence to support this fact that MC attenuated OS in AGEs-induced mesangial cell dysfunction and also in high-glucose-fat diet and STZ-induced DN rats.

scholarly journals Elevated expression of lncRNA MEG3 induces endothelial dysfunction on HUVECs of IVF born offspring via epigenetic regulation

2020 ◽  
Author(s):  
Ying Jiang ◽  
Hong Zhu ◽  
Hong Chen ◽  
Meng-Meng Yang ◽  
Yi-Chen Yu ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Molecular Mechanisms ◽  
Umbilical Vein ◽  
Methylation Status ◽  
Oxidation Products ◽  
Vitro Fertilization ◽  
Elevated Expression ◽  
Nitrite Nitrate

Abstract Background: The cardiovascular dysfunction in children born after in vitro fertilization (IVF) has been of great concern, in our study, we aim to explore potential molecular mechanisms for such long-term outcomes.Methods：Real-time qPCR was used to test long non-coding RNA MEG3 and endothelium-derived factors such as endothelial nitric oxide synthase (eNOS), endothelin-1(ET1), and vascular endothelial growth factor (VEGF). ELISA was used to determinate levels of the first and second oxidation products of NO (nitrite, nitrate), ET1 and VEGF. Primary HUVECs collected after caesarean section were treated with different estradiol concentrations in vitro. Additionally, knockdown of MEG3 on HUVEC provided further evidence between MEG3 expression and alteration of NO, ET1, VEGF. Then, by using pyrosequencing, we uncovered the methylation status of the MEG3 region.Results: We found that the expression level of MEG3 was higher in human umbilical vein endothelial cells (HUVECs) of IVF offspring than that in spontaneously born offspring. Furthermore, we found decreased expression of eNOS and VEGF along with elevated expression of ET1 in HUVECs from IVF offspring compared to spontaneously born offspring, accompanied by lower secretion of nitrite, VEGF, and higher secretion of ET1 in the umbilical cord serum of IVF offspring. We confirmed the results from in vivo experiments by demonstrating that high estradiol intrauterine environments lead to abnormal expression of MEG3 and endothelium derived factors. Meanwhile, silencing MEG3 expression decreased ET1 expression, and increased nitrite, nitrate, and VEGF secretion, which could account for the effects we observed in vivo. With pyrosequencing technology, we found that elevated expression of MEG3 in IVF offspring derived HUVECs was the result of hypomethylation of the MEG3 promoter.Conclusions: Our results demonstrated that increased expression of MEG3 in IVF-born HUVECs, accompanied by lower secretion of eNOS and VEGF along with higher secretion of ET1, which is closely related with endothelial dysfunction, together provide a potential mechanism addressing high risk of hypertension in IVF offspring.

scholarly journals Lipid Peroxidation: A Signaling Mechanism in Diagnosis of Diseases

2021 ◽  
Author(s):  
Kalpana Sabanna Patil ◽  
Raju Ratan Wadekar
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Clinical Practice ◽  
Oxidation Products ◽  
Signaling Mechanism ◽  
Unsaturated Lipids ◽  
End Products ◽  
Lipid Radicals

Quantification of reactive oxygen species, is perplexing either in vivo or in vitro due to their short half-lives. Consequently, to define the magnitude of oxidative stress, the more stable oxidation products can be measured in biological samples. The oxidative stress leads to the lipid peroxidation that involves the initiation, termination and propagation of lipid radicals, wherein, the process involves the oxygen uptake, rearrangement of the double bonds in unsaturated lipids, that leads to polyunsaturated fatty acid deterioration. Subsequently, the toxic signaling end products are considered as biomarkers of free radicals that act both as signaling molecules and as cytotoxic products cause covalent alteration of lipid peroxidation products. The use of validated signaling mechanism (s) of Lipid peroxidation and products derived thereof exhibits its use clinical practice and basic clinical research as well as in clinical practice has become common place, and their presence as endpoints in clinical trials is now broadly accepted. This knowledge can be used to diagnose disease earlier, or to prevent it before it starts. The signaling markers can be used to excel the effectiveness of the prevailing medicines and to improve the new medicines.

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