Abstract 176: Intravenous Infusion Of Glycated End Products Induces Cardiac Remodeling And Fibrosis Through RAGE Mediated Oxidative Stress

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Umadevi Subramanian ◽  
Elangovan Vellaichamy
Keyword(s):  
Oxidative Stress ◽  
Cardiac Remodeling ◽  
Intravenous Infusion ◽  
Lipid Peroxides ◽  
Heart Tissue ◽  
Diabetic Patients ◽  
Long Term Effects ◽  
End Products

Advanced glycation end products (AGEs) play a major role in the development of cardiovascular disorders in diabetic patients. Growing evidence has shown that the western diet is a plentiful source of exogenous AGEs. However, the direct impact of these AGEs on cardiac remodeling process is not well understood. Thus, the present study was intended to scrutinize the long term effects of circulating AGEs on cardiac extracellular matrix alterations both in vivo , Wistar rats, and in vitro , H9C2(2-1) cardiac myofibroblast cells. In vivo Rats (n=8/group) were administered with an intravenous infusion of in vitro prepared glycated-RSA (AGEs-RSA) (50 mg/kg /day for 30 days), while control animals received the non-glycated-RSA. In vitro , H9C2 (2-1) cardiac myofibroblast cells were exposed to AGEs (100µg/ml) for 24 hours. Upon AGEs infusion, a significant increase in fibrosis (3-fold, p<0.01) with increased expression of matrix genes MMP-2 and -9 (P<0.01, respectively), CTGF (p<0.01) and TGF-β (P<0.01) was found in the heart tissues compared to non-glycated-RSA infused rats. Furthermore, an increase in mRNA and protein expression of RAGE (receptor for AGE), and NADPH oxidase (NOX-p47 phox subunit), iNOS and NF-κB was observed in the heart tissue of AGEs infused rats. Furthermore, induction of lipid peroxides (p<0.001) were also found in the heart tissue of AGEs-RSA infused rats. Similarly, H9C2 (2-1) cells exposed to AGEs-RSA demonstrated a significant increase in ROS release (DCF fluorescence, p<0.001) with augmented expression of RAGE ( P <0.01) and NOX-p47 phox ( p <0.001) compared to untreated cells. Whereas, cells pre-treated with N-Acetyl cysteine and RAGE neutralizing antibody significantly impeded the NOX expression ( p <0.01) and attenuated the up-regulation of RAGE and NF-κB in AGEs-RSA treated H9C2 cells. Thus, the results of the present study demonstrated the deleterious effect of AGEs that directly induces oxidative stress and matrix derangement in heart tissue even when ingested through exogenous sources.

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.

scholarly journals S-glutathionylation: relevance in diabetes and potential role as a biomarker

2013 ◽  
Vol 394 (10) ◽  
pp. 1263-1280 ◽  
Author(s):  
Francisco J. Sánchez-Gómez ◽  
Cristina Espinosa-Díez ◽  
Megha Dubey ◽  
Madhu Dikshit ◽  
Santiago Lamas
Keyword(s):  
Oxidative Stress ◽  
Vascular Complications ◽  
Redox Balance ◽  
Diabetic Patients ◽  
Sulfenic Acid ◽  
Diabetic Vascular Complications ◽  
Main Regulator ◽  
Species Production

Abstract Glutathione is considered the main regulator of redox balance in the cellular milieu due to its capacity for detoxifying deleterious molecules. The oxidative stress induced as a result of a variety of stimuli promotes protein oxidation, usually at cysteine residues, leading to changes in their activity. Mild oxidative stress, which may take place in physiological conditions, induces the reversible oxidation of cysteines to sulfenic acid form, while pathological conditions are associated with higher rates of reactive oxygen species production, inducing the irreversible oxidation of cysteines. Among these, neurodegenerative disorders, cardiovascular diseases and diabetes have been proposed to be pathogenetically linked to this state. In diabetes-associated vascular complications, lower levels of glutathione and increased oxidative stress have been reported. S-glutathionylation has been proposed as a posttranslational modification able to protect proteins from over-oxidizing environments. S-glutathionylation has been identified in proteins involved in diabetic models both in vitro and in vivo. In all of them, S-glutathionylation represents a mechanism that regulates the response to diabetic conditions, and has been described to occur in erythrocytes and neutrophils from diabetic patients. However, additional studies are necessary to discern whether this modification represents a biomarker for the early onset of diabetic vascular complications.

scholarly journals Aucubin Protects against Myocardial Infarction-Induced Cardiac Remodeling via nNOS/NO-Regulated Oxidative Stress

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Zheng Yang ◽  
Qing-Qing Wu ◽  
Yang Xiao ◽  
Ming Xia Duan ◽  
Chen Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Cardiac Remodeling ◽  
Coronary Artery Ligation ◽  
No Production ◽  
Protective Effects ◽  
Artery Ligation ◽  
Nos Inhibitors

Whether aucubin could protect myocardial infarction- (MI-) induced cardiac remodeling is not clear. In this study, in a mouse model, cardiac remodeling was induced by left anterior descending coronary artery ligation surgery. Mice were intraperitoneally injected with aucubin (10 mg/kg) 3 days post-MI. Two weeks post-MI, mice in the aucubin treatment group showed decreased mortality, decreased infarct size, and improved cardiac function. Aucubin also decreased cardiac remodeling post-MI. Consistently, aucubin protected cardiomyocytes against hypoxic injury in vitro. Mechanistically, we found that aucubin inhibited the ASK1/JNK signaling. These effects were abolished by the JNK activator. Moreover, we found that the oxidative stress was attenuated in both in vivo aucubin-treated mice heart and in vitro-treated cardiomyocytes, which caused decreased thioredoxin (Trx) consumption, leading to ASK1 forming the inactive complex with Trx. Aucubin increased nNOS-derived NO production in vivo and vitro. The protective effects of aucubin were reversed by the NOS inhibitors L-NAME and L-VINO in vitro. Furthermore, nNOS knockout mice also reversed the protective effects of aucubin on cardiac remodeling. Taken together, aucubin protects against cardiac remodeling post-MI through activation of the nNOS/NO pathway, which subsequently attenuates the ROS production, increases Trx preservation, and leads to inhibition of the ASK1/JNK pathway.

scholarly journals Neither Excessive Nitric Oxide Accumulation nor Acute Hyperglycemia Affects the N-Acetylaspartate Network in Wistar Rat Brain Cells

2020 ◽  
Vol 21 (22) ◽  
pp. 8541
Author(s):  
Marlena Zyśk ◽  
Piotr Pikul ◽  
Robert Kowalski ◽  
Krzysztof Lewandowski ◽  
Monika Sakowicz-Burkiewicz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Wistar Rat ◽  
Diabetic Patients ◽  
Mrna Levels ◽  
Male Adult ◽  
The Impact

The N-acetylaspartate network begins in neurons with N-acetylaspartate production catalyzed by aspartate N-acetyltransferase from acetyl-CoA and aspartate. Clinical studies reported a significant depletion in N-acetylaspartate brain level in type 1 diabetic patients. The main goal of this study was to establish the impact of either hyperglycemia or oxidative stress on the N-acetylaspartate network. For the in vitro part of the study, embryonic rat primary neurons were treated by using a nitric oxide generator for 24 h followed by 6 days of post-treatment culture, while the neural stem cells were cultured in media with 25–75 mM glucose. For the in vivo part, male adult Wistar rats were injected with streptozotocin (65 mg/kg body weight, ip) to induce hyperglycemia (diabetes model) and euthanized 2 or 8 weeks later. Finally, the biochemical profile, NAT8L protein/Nat8l mRNA levels and enzymatic activity were analyzed. Ongoing oxidative stress processes significantly affected energy metabolism and cholinergic neurotransmission. However, the applied factors did not affect the N-acetylaspartate network. This study shows that reduced N-acetylaspartate level in type 1 diabetes is not related to oxidative stress and that does not trigger N-acetylaspartate network fragility. To reveal why N-acetylaspartate is reduced in this pathology, other processes should be considered.

Galectin-3 Mediates Cardiac Remodeling Caused by Impaired Glucose and Lipid Metabolism Through Inhibiting Two Pathways of Activating Akt

2020 ◽  
Author(s):  
Zhen Sun ◽  
Lili Zhang ◽  
Lihua Li ◽  
Chen Shao ◽  
Jia Liu ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Cardiac Remodeling ◽  
Density Lipoprotein ◽  
Myocardial Damage ◽  
Diabetic Patients ◽  
Glucose And Lipid Metabolism ◽  
Lipid Metabolism Disorders ◽  
Galectin 3

Pathological cardiac remodeling is a leading cause of mortality in diabetic patients. Given the glucose and lipid metabolism disorders (GLD) in diabetic patients, it is urgent to conduct a comprehensive study of the myocardial damage under GLD and find key mechanisms. Apolipoprotein E knockout (ApoE-/-) mice, low-density lipoprotein receptor heterozygote (Ldlr+/-) syrian golden hamsters or H9C2 cells were used to construct GLD models -. And GLD significantly promoted cardiomyocyte fibrosis, apoptosis and hypertrophy in vivo and in vitro, while inhibition of galectin-3 (Gal-3) could significantly reverse this process. Then, the signal transmission pathways were determined. It was found that GLD considerably inhibited the phosphorylation of Akt at Thr308 / Ser473, whereas the silencing of Gal-3 could reverse the inhibition of Akt activity through PI3K-AktThr308 and AMPK-mTOR2-AktSer473 pathways. Finally, the PI3K, mTOR, AMPK inhibitor and Akt activator were used to investigate the role of pathways in regulating cardiac remodeling. Phospho-AktThr308 could mediate myocardial fibrosis, while myocardial apoptosis and hypertrophy were regulated by both phospho-AktThr308 and phospho-AktSer473. In conclusion, Gal-3 was an important regulatory factor in GLD-induced cardiac remodeling, and Gal-3 could suppress the phosphorylation of Akt at different sites in mediating cardiomyocyte fibrosis, apoptosis and hypertrophy.

scholarly journals Licochalcone D Ameliorates Oxidative Stress-Induced Senescence via AMPK Activation

2021 ◽  
Vol 22 (14) ◽  
pp. 7324
Author(s):  
Nagarajan Maharajan ◽  
Chitra Devi Ganesan ◽  
Changjong Moon ◽  
Chul-Ho Jang ◽  
Won-Keun Oh ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Tissue ◽  
Ampk Activation ◽  
Expression Levels ◽  
Glycation End Products ◽  
Marrow Mesenchymal Stem Cells ◽  
Cardioprotective Effects ◽  
Double Time

Increased oxidative stress is a crucial factor for the progression of cellular senescence and aging. The present study aimed to investigate the effects of licochalcone D (Lico D) on oxidative stress-induced senescence, both in vitro and in vivo, and explore its potential mechanisms. Hydrogen peroxide (200 µM for double time) and D-galactose (D-Gal) (150 mg/kg) were used to induce oxidative stress in human bone marrow-mesenchymal stem cells (hBM-MSCs) and mice, respectively. We performed the SA-β-gal assay and evaluated the senescence markers, activation of AMPK, and autophagy. Lico D potentially reduced oxidative stress-induced senescence by upregulating AMPK-mediated activation of autophagy in hBM-MSCs. D-Gal treatment significantly increased the expression levels of senescence markers, such as p53 and p21, in the heart and hippocampal tissues, while this effect was reversed in the Lico D-treated animals. Furthermore, a significant increase in AMPK activation was observed in both tissues, while the activation of autophagy was only observed in the heart tissue. Interestingly, we found that Lico D significantly reduced the expression levels of the receptors for advanced glycation end products (RAGE) in the hippocampal tissue. Taken together, our findings highlight the antioxidant, anti-senescent, and cardioprotective effects of Lico D and suggest that the activation of AMPK and autophagy ameliorates the oxidative stress-induced senescence.

scholarly journals Glycation and Advanced Glycation End-Products in Laboratory Experiments in Vivo and in Vitro

2006 ◽  
Vol 49 (1) ◽  
pp. 35-39 ◽  
Author(s):  
Martin Beránek ◽  
Daniela Nováková ◽  
Pavel Rozsíval ◽  
Jaroslav Dršata ◽  
Vladimír Palička
Keyword(s):  
Advanced Glycation End Products ◽  
Incubation Temperature ◽  
Diabetic Patients ◽  
Advanced Glycation ◽  
Glycated Proteins ◽  
Protein Model ◽  
Glycation End Products ◽  
End Products

The purpose of our study was to determine the amount of glycated proteins and advanced glycation end products (AGE) in cataractous lens homogenates of patients who underwent phacoemulsification, and to define a simple in vitro protein model of glycoxidation. Analysis of 30 cataractous lenses (15 diabetic and 15 non-diabetic) revealed a significant increase in both glycated lens proteins of diabetics compared with the controls (0.15 vs 0.08 nmol/mg protein, P < 0.01) and AGE-linked fluorescence at 440 nm (4.8 vs 2.8 AU/mg protein, P < 0.01). The presence of AGE fluorescence in lenses indicates the role of oxidative stress in cataractogenesis. Fifty-six days incubation of alanine and aspartate aminotransferases, used as model proteins, with 500 mM D-fructose at 25 and 37 °C led to a complete inhibition of ALT and AST activities. The fluorescence of both aminotransferases rose according to the chosen incubation temperature: 37 °C > 25 °C > 4 °C. ALT and AST incubated in a medium containing D-fructose are subject to nonenzymatic glycation followed by a consequent formation of AGE products. Our data: i) support the concept of glycation-glycoxidation pathway appearing in diabetic patients; ii) form a base for determination of the efficiency of various antioxidative compounds in vitro.

Abstract 460: Characterization of Glycated Albumin Isolated From Poorly Controlled Diabetic Patients and Its Role in Macrophage Cholesterol Efflux

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Adriana Machado-Lima ◽  
Erika R Oliveira ◽  
Rodrigo T Iborra ◽  
Gabriela Castilho ◽  
Edna R Nakandakare ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Cholesterol Efflux ◽  
Glycated Albumin ◽  
Maldi Mass Spectrometry ◽  
Diabetic Patients ◽  
Advanced Glycation ◽  
Macrophage Cholesterol Efflux

Advanced glycation end products (AGE) are elevated in diabetes mellitus (DM) and predict the development of atherosclerosis. In vitro produced AGE-albumin induces oxidative stress that is linked to the reduction in ABCA-1 levels and cholesterol efflux mediated by apo A-I and HDL-subfractions, leading to macrophage cholesterol accumulation. We characterized the glycation level/profile of human serum albumin (HSA) isolated by fast protein liquid chromatography from poorly controlled type 1 (DM1) and type 2 (DM2) diabetes mellitus patients (HbA1c > 8%) in comparison to control (C) individuals, and how these AGE-albumin can interfere in macrophage lipid accumulation. The glycation level of HSA from C, DM1 and DM2 was analyzed by MALDI mass spectrometry and was similar between DM1 and DM2-HSA. An increased mean mass was observed in DM1-HSA (68,544 ± 192 Da; n=6) and DM2-HSA (68,547 ± 132 Da; n=6) compared to C-HSA (67,846 ± 301 Da; n=6), reflecting the condensation of at least 8 and 5 units of glucose, respectively. The tryptic digestion of C-HSA generated a number of peptide species higher than those originated from DM1 and DM2-HSA. Macrophages isolated from peritoneal wild-type mice were treated for 18 h with C, DM1 or DM2-HSA in order to measure the 14C-cholesterol efflux and the mRNA expression of NOX-4 (NADPHoxidase4), ABCA-1 (Abca1) and ABCG-1 (Abcg1). Data were compared by one-way ANOVA and Dunnet′s post test. In comparison to cells treated with C-HSA the expression of NADPHoxidase4 (p<0.05; n=3) mRNA was increased after cell treatment with DM1 (3.2x) and DM2-HSA (0.7x), confirming oxidative stress. Abcg1 mRNA was reduced by DM2-HSA (26%; p<0.05; n=3); Abca1 mRNA was unchanged but ABCA-1 protein content was greatly reduced (82 and 25%, respectively in DM1 and DM2-HAS; p<0.05; n=12). The % of apo A-I mediated cholesterol efflux was impaired in DM1 (1.3 ± 0.3) and DM2-HSA-treated cells (2.4 ± 0.5) as compared to C-HSA (4.4 ± 0.5; n= 5; p<0.05). The level of advanced glycation that takes place in vivo was similar between DM1 and DM2-HSA and induced macrophage oxidative stress and impairment in cholesterol efflux that may contribute to atherogenesis in DM. Funding: FAPESP, Brazil (2012/19112-0)

scholarly journals The influence of natural dicarbonils on the antioxidant enzymes activity in vitro and in vivo

2012 ◽  
Vol 58 (6) ◽  
pp. 727-736 ◽  
Author(s):  
V.Z. Lankin ◽  
G.G. Konovalova ◽  
A.K. Tikhaze ◽  
L.V. Nedosugova
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Antioxidant Enzymes ◽  
Carbonyl Stress ◽  
Diabetic Patients ◽  
Glutathione S Transferase ◽  
Liver Glutathione ◽  
Bovine Erythrocytes

Natural dicarbonyls, which may be accumulated during oxidative stress in atherosclerosis (e.g. malondialdehyde) or carbonyl stress in diabetes mellitus (glyoxal and methylglyoxal) effectively inhibited the activities of commercial preparations of antioxidant enzymes: catalase, Cu,Zn-superoxide dismutase (Cu,Zn-SOD) and Se-contained glutathione peroxidase from human and bovine erythrocytes and also rat liver glutathione-S-transferase. After incubation of human erythrocytes with 10 mM of each investigated dicarbonyls the decrease of intracellular Cu,Zn-SOD was observed. The decreased activity of erythrocyte Cu,Zn-SOD was also detected in diabetic patients with carbohydrate metabolism disturbance but effective sugar-lowered therapy was accompanied by the increase of this enzyme activity. The increase of erythrocytes activity of Cu,Zn-SOD of diabetic patients theated with metformin (which may utilize methylglyoxal) was higher than in erythrocytase of diabetic patients subjected to traditional therapy.

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