scholarly journals Oxidative, Reductive, and Nitrosative Stress Effects on Epigenetics and on Posttranslational Modification of Enzymes in Cardiometabolic Diseases

2020 ◽  
Vol 2020 ◽  
pp. 1-19
Author(s):  
I. Pérez-Torres ◽  
M. E. Soto ◽  
V. Castrejón-Tellez ◽  
M. E. Rubio-Ruiz ◽  
L. Manzano Pech ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Nitrosative Stress ◽  
Adult Life ◽  
Antioxidant Systems ◽  
Amino Acid Residues ◽  
Cardiometabolic Diseases ◽  
Stress Effects ◽  
Cardiometabolic Disorders ◽  
Dna Reparation ◽  
The Impact

Oxidative (OS), reductive (RS), and nitrosative (NSS) stresses produce carbonylation, glycation, glutathionylation, sulfhydration, nitration, and nitrosylation reactions. OS, RS, and NSS are interrelated since RS results from an overactivation of antioxidant systems and NSS is the result of the overactivation of the oxidation of nitric oxide (NO). Here, we discuss the general characteristics of the three types of stress and the way by which the reactions they induce (a) damage the DNA structure causing strand breaks or inducing the formation of 8-oxo-d guanosine; (b) modify histones; (c) modify the activities of the enzymes that determine the establishment of epigenetic cues such as DNA methyl transferases, histone methyl transferases, acetyltransferases, and deacetylases; (d) alter DNA reparation enzymes by posttranslational mechanisms; and (e) regulate the activities of intracellular enzymes participating in metabolic reactions and in signaling pathways through posttranslational modifications. Furthermore, the three types of stress may establish new epigenetic marks through these reactions. The development of cardiometabolic disorders in adult life may be programed since early stages of development by epigenetic cues which may be established or modified by OS, RS, and NSS. Therefore, the three types of stress participate importantly in mediating the impact of the early life environment on later health and heritability. Here, we discuss their impact on cardiometabolic diseases. The epigenetic modifications induced by these stresses depend on union and release of chemical residues on a DNA sequence and/or on amino acid residues in proteins, and therefore, they are reversible and potentially treatable.

scholarly journals Nitrosative Stress and Its Association with Cardiometabolic Disorders

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2555 ◽  
Author(s):  
Israel Pérez-Torres ◽  
Linaloe Manzano-Pech ◽  
María Esther Rubio-Ruíz ◽  
María Elena Soto ◽  
Verónica Guarner-Lans
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Nitrosative Stress ◽  
Current Knowledge ◽  
Redox System ◽  
Nitrogen Species ◽  
Irreversible Damage ◽  
Cardiometabolic Diseases ◽  
Cardiometabolic Disorders ◽  
Oxide Synthase

Reactive nitrogen species (RNS) are formed when there is an abnormal increase in the level of nitric oxide (NO) produced by the inducible nitric oxide synthase (iNOS) and/or by the uncoupled endothelial nitric oxide synthase (eNOS). The presence of high concentrations of superoxide anions (O2−) is also necessary for their formation. RNS react three times faster than O2− with other molecules and have a longer mean half life. They cause irreversible damage to cell membranes, proteins, mitochondria, the endoplasmic reticulum, nucleic acids and enzymes, altering their activity and leading to necrosis and to cell death. Although nitrogen species are important in the redox imbalance, this review focuses on the alterations caused by the RNS in the cellular redox system that are associated with cardiometabolic diseases. Currently, nitrosative stress (NSS) is implied in the pathogenesis of many diseases. The mechanisms that produce damage remain poorly understood. In this paper, we summarize the current knowledge on the participation of NSS in the pathology of cardiometabolic diseases and their possible mechanisms of action. This information might be useful for the future proposal of anti-NSS therapies for cardiometabolic diseases.

Abstract 18346: Transcriptional Characterization of Glo1 Knockdown and Transgenic Mouse Models Implies a Role in Cardiometabolic Diseases

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Le Shu ◽  
Richard C Davis ◽  
Xiuju Wu ◽  
Aldons J Lusis ◽  
Abraham A Palmer ◽  
...  
Keyword(s):  
Animal Models ◽  
Gene Network ◽  
Transcriptional Profiling ◽  
Protective Role ◽  
Integrative Genomics ◽  
Significant Differential Expression ◽  
Collagen Formation ◽  
Cardiometabolic Diseases ◽  
Cardiometabolic Disorders ◽  
The Impact

Accumulation of advanced glycation end-products (AGEs) has been associated with atherosclerosis and diabetes. As the major detoxifying enzyme for AGE precursors, Glyoxalase 1 (Glo1) has been implicated in diabetic complications and more recently in coronary artery disease (CAD). We have recently identified Glo1 as a potential key regulator for an antigen-related gene network that is causal for CAD through an integrative genomics analysis. However, whether Glo1 plays a protective role against cardiometabolic disorders remains controversial. To systematically investigate the impact of Glo1, we performed genome-wide transcriptional profiling of two genetically modified animal models with either Glo1 overexpression in a transgenic (TG) model or Glo1 knockdown (KD), both on C57BL/6J background. For each mouse model, we examined the liver, aorta, adipose and kidney tissues. We found that the Glo1 KD mice which had ~50% reduced Glo1 expression showed much stronger perturbation at transcriptomic level, as compared to Glo1 TG mice. For Glo1 KD mice, significant differential expression was observed across tissues for multiple known cardiometabolic risk genes, including Ide, Cdkn2b and Col4a1, as well as perturbations of lipid metabolic pathways such as PPAR signaling and fatty acid metabolism. We also identified iron transport and collagen formation pathways as specifically enriched in the differentially expressed genes in aorta. When intersected with human GWAS, the Glo1 KD signature genes were found to be enriched for candidate genes associated with lipid levels, type 2 diabetes and coronary heart disease. Lastly, genes perturbed in the Glo1 KD animals had significant overlap with our predicted CAD-antigen gene network in both aorta (p = 0.005) and liver (p = 0.03). This study suggests a functional role of Glo1 in regulating multiple processes relevant to cardiometabolic diseases. Future investigation of these animal models in atherogenesis under diabetic conditions is warranted.

Pigment Epithelium-Derived Factor: A Novel Therapeutic Target for Cardiometabolic Diseases and Related Complications

2018 ◽  
Vol 25 (13) ◽  
pp. 1480-1500 ◽  
Author(s):  
Sho-ichi Yamagishi ◽  
Takanori Matsui
Keyword(s):  
Cardiovascular Disease ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Visceral Obesity ◽  
Retinal Pigment Epithelial Cells ◽  
Atherosclerotic Cardiovascular Disease ◽  
Cardiometabolic Diseases ◽  
The Metabolic Syndrome ◽  
Pigment Epithelium Derived Factor ◽  
Cardiometabolic Disorders

Pigment epithelium-derived factor (PEDF) is a glycoprotein that belongs to the superfamily of serine protease inhibitors, serpins. It was first identified as a neuronal differentiating factor secreted by human retinal pigment epithelial cells, and then found to be the most potent inhibitor of pathological angiogenesis in mammalian eyes. Recently, PEDF has been shown not only to suppress oxidative stress and inflammatory reactions in vascular wall cells, T cells and macrophages, and adipocytes, but also to exert antithrombotic and anti-fibrotic properties, thereby protecting against the development and progression of various cardiometabolic diseases and related complications. Furthermore, accumulating evidence has suggested that circulating PEDF levels may be a biomarker of severity and prognosis of these devastating disorders. Number of subjects with visceral obesity and insulin resistance is increasing, and the metabolic syndrome and its related complications, such as diabetes, nonalcoholic fatty liver disease/non-alcoholic steatohepatits, and atherosclerotic cardiovascular disease are a growing health challenge. Therefore, in this study, we review the pathophysiological role of PEDF in obesity and metabolic disorders, cardiovascular disease, diabetic eye and kidney complications, liver diseases, and reproductive system disorders, and discuss the potential clinical utility of modulating the expression and actions of PEDF for preventing these cardiometabolic disorders. We also refer to the clinical value of PEDF as a biomarker in cardiometabolic complications.

scholarly journals Developmental up-regulation of NMDA receptors in the prefrontal cortex and hippocampus of mGlu5 receptor knock-out mice

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Tiziana Imbriglio ◽  
Remy Verhaeghe ◽  
Nico Antenucci ◽  
Stefania Maccari ◽  
Giuseppe Battaglia ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Nmda Receptor ◽  
Metabotropic Glutamate Receptors ◽  
Adult Life ◽  
Developmental Time ◽  
Postnatal Life ◽  
Developmental Studies ◽  
Knock Out ◽  
Nmda Receptor Subunits ◽  
The Impact

AbstractmGlu5 metabotropic glutamate receptors are highly expressed and functional in the early postnatal life, and are known to positively modulate NMDA receptor function. Here, we examined the expression of NMDA receptor subunits and interneuron-related genes in the prefrontal cortex and hippocampus of mGlu5−/− mice and wild-type littermates at three developmental time points (PND9, − 21, and − 75). We were surprised to find that expression of all NMDA receptor subunits was greatly enhanced in mGlu5−/− mice at PND21. In contrast, at PND9, expression of the GluN2B subunit was enhanced, whereas expression of GluN2A and GluN2D subunits was reduced in both regions. These modifications were transient and disappeared in the adult life (PND75). Changes in the transcripts of interneuron-related genes (encoding parvalbumin, somatostatin, vasoactive intestinal peptide, reelin, and the two isoforms of glutamate decarboxylase) were also observed in mGlu5−/− mice across postnatal development. For example, the transcript encoding parvalbumin was up-regulated in the prefrontal cortex of mGlu5−/− mice at PND9 and PND21, whereas it was significantly reduced at PND75. These findings suggest that in mGlu5−/− mice a transient overexpression of NMDA receptor subunits may compensate for the lack of the NMDA receptor partner, mGlu5. Interestingly, in mGlu5−/− mice the behavioral response to the NMDA channel blocker, MK-801, was significantly increased at PND21, and largely reduced at PND75. The impact of adaptive changes in the expression of NMDA receptor subunits should be taken into account when mGlu5−/− mice are used for developmental studies.

Decline of contractility during ischemia-reperfusion injury: actin glutathionylation and its effect on allosteric interaction with tropomyosin

2006 ◽  
Vol 290 (3) ◽  
pp. C719-C727 ◽  
Author(s):  
Frank C. Chen ◽  
Ozgur Ogut
Keyword(s):  
Reperfusion Injury ◽  
Posttranslational Modifications ◽  
Actin Polymerization ◽  
Time Course ◽  
Troponin I ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
High Concentration ◽  
Cross Sectional ◽  
The Impact

The severity and duration of ischemia-reperfusion injury is hypothesized to play an important role in the ability of the heart subsequently to recover contractility. Permeabilized trabeculae were prepared from a rat model of ischemia-reperfusion injury to examine the impact on force generation. Compared with the control perfused condition, the maximum force (Fmax) per cross-sectional area and the rate of tension redevelopment of Ca2+-activated trabeculae fell by 71% and 44%, respectively, during ischemia despite the availability of a high concentration of ATP. The reduction in Fmax with ischemia was accompanied by a decline in fiber stiffness, implying a drop in the absolute number of attached cross bridges. However, the declines during ischemia were largely recovered after reperfusion, leading to the hypothesis that intrinsic, reversible posttranslational modifications to proteins of the contractile filaments occur during ischemia-reperfusion injury. Examination of thin-filament proteins from ischemic or ischemia-reperfused hearts did not reveal proteolysis of troponin I or T. However, actin was found to be glutathionylated with ischemia. Light-scattering experiments demonstrated that glutathionylated G-actin did not polymerize as efficiently as native G-actin. Although tropomyosin accelerated the time course of native and glutathionylated G-actin polymerization, the polymerization of glutathionylated G-actin still lagged native G-actin at all concentrations of tropomyosin tested. Furthermore, cosedimentation experiments demonstrated that tropomyosin bound glutathionylated F-actin with significantly reduced cooperativity. Therefore, glutathionylated actin may be a novel contributor to the diverse set of posttranslational modifications that define the function of the contractile filaments during ischemia-reperfusion injury.

scholarly journals Risk factors for physical inactivity across the adult life span: the impact of depression

2006 ◽  
Vol 18 (6) ◽  
pp. 274-274
Author(s):  
J Walker ◽  
H Christensen ◽  
T Windsor ◽  
A George
Keyword(s):  
Risk Factors ◽  
Life Span ◽  
Physical Inactivity ◽  
Adult Life ◽  
Adult Life Span ◽  
The Impact

scholarly journals Novel antibody binding determinants on the capsid surface of serotype O foot-and-mouth disease virus

2014 ◽  
Vol 95 (5) ◽  
pp. 1104-1116 ◽  
Author(s):  
Amin S. Asfor ◽  
Sasmita Upadhyaya ◽  
Nick J. Knowles ◽  
Donald P. King ◽  
David J. Paton ◽  
...  
Keyword(s):  
Amino Acid ◽  
Guinea Pig ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Amino Acid Residues ◽  
Serotype O ◽  
Antigenic Sites ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
The Impact

Five neutralizing antigenic sites have been described for serotype O foot-and-mouth disease viruses (FMDV) based on monoclonal antibody (mAb) escape mutant studies. However, a mutant virus selected to escape neutralization of mAb binding at all five sites was previously shown to confer complete cross-protection with the parental virus in guinea pig challenge studies, suggesting that amino acid residues outside the mAb binding sites contribute to antibody-mediated in vivo neutralization of FMDV. Comparison of the ability of bovine antisera to neutralize a panel of serotype O FMDV identified three novel putative sites at VP2-74, VP2-191 and VP3-85, where amino acid substitutions correlated with changes in sero-reactivity. The impact of these positions was tested using site-directed mutagenesis to effect substitutions at critical amino acid residues within an infectious copy of FMDV O1 Kaufbeuren (O1K). Recovered viruses containing additional mutations at VP2-74 and VP2-191 exhibited greater resistance to neutralization with both O1K guinea pig and O BFS bovine antisera than a virus that was engineered to include only mutations at the five known antigenic sites. The changes at VP2-74 and VP3-85 are adjacent to critical amino acids that define antigenic sites 2 and 4, respectively. However VP2-191 (17 Å away from VP2-72), located at the threefold axis and more distant from previously identified antigenic sites, exhibited the most profound effect. These findings extend our knowledge of the surface features of the FMDV capsid known to elicit neutralizing antibodies, and will improve our strategies for vaccine strain selection and rational vaccine design.

Caracole as a Potential Neuroprotective Agent for Neurological Diseases: A Systematic

2021 ◽  
Vol 20 ◽  
Author(s):  
Mohammad Zamanian ◽  
Małgorzata Kujawska ◽  
Marjan Nikbakht Zadeh ◽  
Amin Hassanshahi ◽  
Soudeh Ramezanpour ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Traumatic Brain Injury ◽  
Parkinson's Disease ◽  
Brain Injury ◽  
Neurological Diseases ◽  
Antioxidant Systems ◽  
Neuroprotective Agent ◽  
The Impact

Background & objective: Neurological diseases are becoming a significant problem worldwide, with the elderly at a higher risk of being affected. Several researchers have investigated the neuroprotective effects of Carvacrol (CAR) (5-isopropyl-2-methyl phenol). This review systematically surveys the existing literature on the impact of CAR when used as a neuroprotective agent in neurological diseases. Methods: The systematic review involved English articles published in the last ten years obtained from PubMed, Google Scholar, and Scopus databases. The following descriptors were used to search the literature: “Carvacrol” [Title] AND “neuroprotective (neuroprotection)” [Title] OR “stroke, traumatic brain injury, Alzheimer's disease, Parkinson's disease, seizure, epilepsy [Title]. Results: : A total of 208 articles were retrieved during the search process, but only 20 studies met the eligibility criteria and were included for review. A total of 20 articles were identified, in which the efficacy of CAR was described in experimental models of stroke, traumatic brain injury, Parkinson’s disease, Alzheimer’s disease, , epilepsy, and seizure, through motor deficits improvements in neurochemical activity, especially antioxidant systems, reducing inflammation, oxidative stress and apoptosis as well as inhibition of TRPC1 and TRPM7. Conclusion : The data presented in this study support the beneficial impact of CAR on behavioural and neurochemical deficits. CAR benefits accrue because of its anti-apoptotic, antioxidant, and anti-inflammatory properties. Therefore, CAR has emerged as an alternative treatment for neurological disorders based on its properties.

scholarly journals The impact of neighborhood walkability on walking: Does it differ across adult life stage and does neighborhood buffer size matter?

2014 ◽  
Vol 25 ◽  
pp. 43-46 ◽  
Author(s):  
Karen Villanueva ◽  
Matthew Knuiman ◽  
Andrea Nathan ◽  
Billie Giles-Corti ◽  
Hayley Christian ◽  
...  
Keyword(s):  
Life Stage ◽  
Adult Life ◽  
Buffer Size ◽  
Neighborhood Walkability ◽  
Size Matter ◽  
The Impact

scholarly journals Molecular Docking Senyawa Gingerol dan Zingiberol pada Tanaman Jahe sebagai Penanganan COVID-19

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Belinda D. P. M. Ratu ◽  
Widdhi Bodhi ◽  
Fona Budiarso ◽  
Billy J. Kepel ◽  
. Fatimawali ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Amino Acid Residues ◽  
Autodock Vina ◽  
Discovery Studio ◽  
Main Protease ◽  
Docking Method ◽  
Pubmed Database ◽  
Almost All ◽  
The Impact

Abstract: COVID-19 is a new disease. Many people feel the impact of this disease. There is no definite cure for COVID-19, so many people use traditional medicine to ward off COVID-19, including ginger. This study aims to determine whether there is an interaction between compounds in ginger (gingerol and zingiberol) and the COVID-19’s main protease (6LU7). This study uses a molecular docking method using 4 main applications, namely Autodock Tools, Autodock Vina, Biovia Discovery Studio 2020, and Open Babel GUI. The samples used were gingerol and zingiberol compounds in ginger plants downloaded from Pubchem. The data used in this study used Mendeley, Clinical Key, and PubMed database. The study showed that almost all of the amino acid residues in the gingerol compound acted on the 6LU7 active site, whereas the zingiberol did not. The results of the binding affinity of ginger compounds, both gingerol and zingiberol, do not exceed the binding affinity of remdesivir, a drug that is widely researched as a COVID-19 handling drug. In conclusion, gingerol and zingiberol compounds in ginger can’t be considered as COVID-19’s treatment.Keywords: molecular docking, gingerol, zingiberol Abstrak: COVID-19 merupakan sebuah penyakit yang baru. Banyak masyarakat yang merasakan dampak dari penyakit ini. Belum ada pengobatan pasti untuk menyembuhkan COVID-19, sehingga banyak masyarakat yang menggunakan pengobatan tradisional untuk menangkal COVID-19, termasuk jahe. Penelitian ini bertujuan untuk mengetahui apakah ada interaksi antara senyawa pada jahe (gingerol dan zingiberol) dengan main protease COVID-19 (6LU7). Penelitian ini menggunakan metode molecular docking dengan menggunakan 4 aplikasi utama, yaitu Autodock Tools, Autodock Vina, Biovia Discovery Studio 2020, dan Open Babel GUI. Sampel yang digunakan yaitu senyawa gingerol dan zingiberol pada tanaman jahe yang diunduh di Pubchem. Data yang digunakan dalam penelitian ini menggunakan database Mendeley, Clinical Key, dan PubMed. Penelitian menunjukkan bahwa hampir semua residu asam amino pada senyawa gingerol bekerja pada sisi aktif 6LU7, sedangkan tidak demikian pada zingiberol. Hasil binding affinity senyawa jahe, baik gingerol maupun zingiberol tidak  melebihi binding affinity remdesivir, obat yang banyak diteliti sebagai obat penanganan COVID-19. Sebagai simpulan, senyawa gingerol dan zingiberol pada tanaman jahe tidak dapat dipertimbangkan sebagai penanganan COVID-19Kata Kunci: molecular docking, gingerol, zingiberol

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