scholarly journals Glyoxalase System as a Therapeutic Target against Diabetic Retinopathy

Antioxidants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1062 ◽  
Author(s):  
Gemma Aragonès ◽  
Sheldon Rowan ◽  
Sarah G Francisco ◽  
Wenxin Yang ◽  
Jasper Weinberg ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Retinopathy ◽  
Therapeutic Strategy ◽  
Diabetic Complication ◽  
Wild Type ◽  
Glyoxalase System ◽  
Age Related ◽  
Glycation End Products ◽  
Working Age ◽  
Stress Formation

Hyperglycemia, a defining characteristic of diabetes, combined with oxidative stress, results in the formation of advanced glycation end products (AGEs). AGEs are toxic compounds that have adverse effects on many tissues including the retina and lens. AGEs promote the formation of reactive oxygen species (ROS), which, in turn, boost the production of AGEs, resulting in positive feedback loops, a vicious cycle that compromises tissue fitness. Oxidative stress and the accumulation of AGEs are etiologically associated with the pathogenesis of multiple diseases including diabetic retinopathy (DR). DR is a devastating microvascular complication of diabetes mellitus and the leading cause of blindness in working-age adults. The onset and development of DR is multifactorial. Lowering AGEs accumulation may represent a potential therapeutic approach to slow this sight-threatening diabetic complication. To set DR in a physiological context, in this review we first describe relations between oxidative stress, formation of AGEs, and aging in several tissues of the eye, each of which is associated with a major age-related eye pathology. We summarize mechanisms of AGEs generation and anti-AGEs detoxifying systems. We specifically feature the potential of the glyoxalase system in the retina in the prevention of AGEs-associated damage linked to DR. We provide a comparative analysis of glyoxalase activity in different tissues from wild-type mice, supporting a major role for the glyoxalase system in the detoxification of AGEs in the retina, and present the manipulation of this system as a therapeutic strategy to prevent the onset of DR.

scholarly journals Circulating Biomarkers of Diabetic Retinopathy: An Overview Based on Physiopathology

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Olga Simó-Servat ◽  
Rafael Simó ◽  
Cristina Hernández
Keyword(s):  
Diabetic Retinopathy ◽  
Therapeutic Strategy ◽  
New Drugs ◽  
Diagnostic Tools ◽  
Diabetic Patients ◽  
Circulating Biomarkers ◽  
Pharmacological Treatments ◽  
Early Stages ◽  
Working Age ◽  
Advanced Stages

Diabetic retinopathy (DR) is the main cause of working-age adult-onset blindness. The currently available treatments for DR are applicable only at advanced stages of the disease and are associated with significant adverse effects. In early stages of DR the only therapeutic strategy that physicians can offer is a tight control of the risk factors for DR. Therefore, new pharmacological treatments for these early stages of the disease are required. In order to develop therapeutic strategies for early stages of DR new diagnostic tools are urgently needed. In this regard, circulating biomarkers could be useful to detect early disease, to identify those diabetic patients most prone to progressive worsening who ought to be followed up more often and who could obtain the most benefit from these therapies, and to monitor the effectiveness of new drugs for DR before more advanced DR stages have been reached. Research of biomarkers for DR has been mainly based on the pathogenic mechanism involved in the development of DR (i.e., AGEs, oxidative stress, endothelial dysfunction, inflammation, and proangiogenic factors). This review focuses on circulating biomarkers at both early and advanced stages that could be relevant for the prediction or detection of DR.

Abstract 123: Age-Related Endothelial Senescence is Driven by Thrombospondin-1-Activated NADPH Oxidase Nox1

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Daniel N Meijles ◽  
Imad Al Ghouleh ◽  
Sanghamitra Sahoo ◽  
Jefferson H Amaral ◽  
Heather Knupp ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Vascular Diseases ◽  
Dependent Manner ◽  
Wild Type ◽  
Molecular Control ◽  
Redox Biology ◽  
Age Related ◽  
P53 Activation

Organismal aging represents an independent risk factor underlying many vascular diseases, including systemic and pulmonary hypertension, and atherosclerosis. While the mechanisms driving aging are largely elusive, a steady persistent increase in tissue oxidative stress has been associated with senescence. Previously we showed TSP1 elicits NADPH oxidase (Nox)-dependent vascular smooth muscle cell oxidative stress. However mechanisms by which TSP1 affects endothelial redox biology are unknown. Here, we tested the hypothesis that TSP1 induces endothelial oxidative stress-linked senescence in aging. Using rapid autopsy disease-free human pulmonary (PA) artery, we identified a significant positive correlation between age, protein levels of TSP1, Nox1 and the cell-cycle repressor p21cip (p<0.05). Age also positively associated with increased Amplex Red-detected PA hydrogen peroxide levels (p<0.05). Moreover, treatment of human PA endothelial cells (HPAEC) with TSP1 (2.2nM; 24h) increased expression (~1.9 fold; p<0.05) and activation of Nox1 (~1.7 fold; p<0.05) compared to control, as assessed by Western blot and SOD-inhibitable cytochrome c reduction. Western blotting and immunofluorescence showed a TSP1-mediated increase in p53 activation, indicative of the DNA damage response. Moreover, TSP1 significantly increased HPAEC senescence in a p53/p21cip/Rb-dependent manner, as assessed by immunofluorescent detection of subcellular localization and senescence-associated β-galactosidase staining. To explore this pathway in vivo, middle-aged (8-10 month) wild-type and TSP1-null mice were utilized. In the TSP1-null, reduced lung senescence, oxidative stress, Nox1 levels and p21cip expression were observed compared to wild-type supporting findings in human samples and cell experiments. Finally, prophylactic treatment with specific Nox1 inhibitor NoxA1ds (10μM) attenuated TSP1-induced HPAEC ROS, p53 activation, p21cip expression and senescence. Taken together, our results provide molecular insight into the functional interplay between TSP1 and Nox1 in the regulation of endothelial senescence, with implications for molecular control of the aging process.

scholarly journals Methylglyoxal, a Highly Reactive Dicarbonyl Compound, in Diabetes, Its Vascular Complications, and Other Age-Related Diseases

2020 ◽  
Vol 100 (1) ◽  
pp. 407-461 ◽  
Author(s):  
C. G. Schalkwijk ◽  
C. D. A. Stehouwer
Keyword(s):  
Inflammatory Diseases ◽  
Vascular Complications ◽  
Glyoxalase System ◽  
Dicarbonyl Compound ◽  
Complications Of Diabetes ◽  
Age Related ◽  
Glycation End Products ◽  
New Directions ◽  
The Central Nervous System

The formation and accumulation of methylglyoxal (MGO), a highly reactive dicarbonyl compound, has been implicated in the pathogenesis of type 2 diabetes, vascular complications of diabetes, and several other age-related chronic inflammatory diseases such as cardiovascular disease, cancer, and disorders of the central nervous system. MGO is mainly formed as a byproduct of glycolysis and, under physiological circumstances, detoxified by the glyoxalase system. MGO is the major precursor of nonenzymatic glycation of proteins and DNA, subsequently leading to the formation of advanced glycation end products (AGEs). MGO and MGO-derived AGEs can impact on organs and tissues affecting their functions and structure. In this review we summarize the formation of MGO, the detoxification of MGO by the glyoxalase system, and the biochemical pathways through which MGO is linked to the development of diabetes, vascular complications of diabetes, and other age-related diseases. Although interventions to treat MGO-associated complications are not yet available in the clinical setting, several strategies to lower MGO have been developed over the years. We will summarize several new directions to target MGO stress including glyoxalase inducers and MGO scavengers. Targeting MGO burden may provide new therapeutic applications to mitigate diseases in which MGO plays a crucial role.

scholarly journals Effect of Lutein and Antioxidant Supplementation on VEGF Expression, MMP-2 Activity, and Ultrastructural Alterations in Apolipoprotein E-Deficient Mouse

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Patricia Fernández-Robredo ◽  
Luis M. Sádaba ◽  
Angel Salinas-Alamán ◽  
Sergio Recalde ◽  
José A. Rodríguez ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Age Related Macular Degeneration ◽  
Membrane Thickness ◽  
Wild Type ◽  
Vegf Expression ◽  
Morphological Alterations ◽  
Ultrastructural Alterations ◽  
Age Related ◽  
Deficient Mice ◽  
Expression And Activity

Oxidative stress is involved in the pathogenesis of several diseases such as atherosclerosis and age-related macular degeneration (AMD). ApoE-deficient mice (apoE−/−) are a well-established model of genetic hypercholesterolemia and develop retinal alterations similar to those found in humans with AMD. Thus supplementation with lutein or multivitamin plus lutein and glutathione complex (MV) could prevent the onset of these alterations. ApoE−/−mice (n=40, 3 months old) were treated daily for 3 months with lutein (AE-LUT) or MV (two doses): AE-MV15 (15 mg/kg/day) and AE-MV50 (50 mg/kg/day) and were compared to controls with vehicle (AE-C). Wild-type mice (n=10) were also used as control (WT-C). ApoE−/−mice showed higher retinal lipid peroxidation and increased VEGF expression and MMP-2 activity, associated with ultrastructural alterations such as basal laminar deposits, vacuoles, and an increase in Bruch's membrane thickness. While lutein alone partially prevented the alterations observed in apoE−/−mice, MV treatment substantially reduced VEGF levels and MMP-2 activity and ameliorated the retinal morphological alterations. These results suggest that oxidative stress in addition to an increased expression and activity of proangiogenic factors could participate in the onset or development of retinal alterations of apoE−/−mice. Moreover, these changes could be prevented by efficient antioxidant treatments.

scholarly journals Vitamin B12 in Relation to Oxidative Stress: A Systematic Review

Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 482 ◽  
Author(s):  
Erik van de Lagemaat ◽  
Lisette de Groot ◽  
Ellen van den Heuvel
Keyword(s):  
Oxidative Stress ◽  
Vitamin B12 ◽  
Antioxidant Properties ◽  
Micronutrient Deficiencies ◽  
Ros Scavenging ◽  
Stress Markers ◽  
Age Related ◽  
Glycation End Products ◽  
Growth Factor Production ◽  
Randomised Controlled

The triage theory posits that modest micronutrient deficiencies may induce reallocation of nutrients to processes necessary for immediate survival at the expense of long-term health. Neglected processes could in time contribute to the onset of age-related diseases, in which oxidative stress is believed to be a major factor. Vitamin B12 (B12) appears to possess antioxidant properties. This review aims to summarise the potential antioxidant mechanisms of B12 and investigate B12 status in relation to oxidative stress markers. A systematic query-based search of PubMed was performed to identify eligible publications. The potential antioxidant properties of B12 include: (1) direct scavenging of reactive oxygen species (ROS), particularly superoxide; (2) indirect stimulation of ROS scavenging by preservation of glutathione; (3) modulation of cytokine and growth factor production to offer protection from immune response-induced oxidative stress; (4) reduction of homocysteine-induced oxidative stress; and (5) reduction of oxidative stress caused by advanced glycation end products. Some evidence appears to suggest that lower B12 status is related to increased pro-oxidant and decreased antioxidant status, both overall and for subclinically deficient individuals compared to those with normal B12 status. However, there is a lack of randomised controlled trials and prospective studies focusing specifically on the relation between B12 and oxidative stress in humans, resulting in a low strength of evidence. Further work is warranted.

scholarly journals Cacao powder supplementation attenuates oxidative stress, cholinergic impairment, and apoptosis in d-galactose-induced aging rat brain

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hyoeun Yoo ◽  
Hyun-Sook Kim
Keyword(s):  
Oxidative Stress ◽  
Control Group ◽  
Protective Effects ◽  
Aging Male ◽  
Sprague Dawley ◽  
Advanced Glycation ◽  
Age Related ◽  
Sprague Dawley Rats ◽  
Glycation End Products ◽  
Aging Rat

AbstractAging, a critical risk factor of several diseases, including neurodegenerative disorders, affects an ever-growing number of people. Cacao supplementation has been suggested to improve age-related neuronal deficits. Therefore, this study investigated the protective effects of raw cacao powder on oxidative stress-induced aging. Male Sprague–Dawley rats were divided into 4 groups: Control (C), d-galactose-induced aging (G), d-galactose injection with 10% (LC), and 16% (HC) cacao powder mixed diet. d-galactose (300 mg/3 mL/kg) was intraperitoneally injected into all but the control group for 12 weeks. Cacao supplemented diets were provided for 8 weeks. The levels of serum Malondialdehyde (MDA), Advanced Glycation End-products (AGEs), brain and liver MDA, the indicators of the d-galactose induced oxidative stress were significantly decreased in LC and HC but increased in G. The Acetylcholinesterase (AChE) activity of brain showed that the cholinergic impairment was significantly lower in LC, and HC than G. Furthermore, the expression levels of catalase (CAT), phospho-Akt/Akt, and procaspase-3 were significantly increased in LC and HC. In conclusion, cacao consumption attenuated the effects of oxidative stress, cholinergic impairment and apoptosis, indicating its potential in future clinical studies.

scholarly journals Progerin Expression Induces Inflammation, Oxidative Stress and Senescence in Human Coronary Endothelial Cells

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1201 ◽  
Author(s):  
Guillaume Bidault ◽  
Marie Garcia ◽  
Jacqueline Capeau ◽  
Romain Morichon ◽  
Corinne Vigouroux ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Endothelial Dysfunction ◽  
Premature Aging ◽  
Lamin A ◽  
Wild Type ◽  
Human Endothelial Cells ◽  
Endothelial Cell Function ◽  
Age Related

Hutchinson–Gilford progeria syndrome (HGPS) is a rare premature aging disorder notably characterized by precocious and deadly atherosclerosis. Almost 90% of HGPS patients carry a LMNA p.G608G splice variant that leads to the expression of a permanently farnesylated abnormal form of prelamin-A, referred to as progerin. Endothelial dysfunction is a key determinant of atherosclerosis, notably during aging. Previous studies have shown that progerin accumulates in HGPS patients’ endothelial cells but also during vascular physiological aging. However, whether progerin expression in human endothelial cells can recapitulate features of endothelial dysfunction is currently unknown. Herein, we evaluated the direct impact of exogenously expressed progerin and wild-type lamin-A on human endothelial cell function and senescence. Our data demonstrate that progerin, but not wild-type lamin-A, overexpression induces endothelial cell dysfunction, characterized by increased inflammation and oxidative stress together with persistent DNA damage, increased cell cycle arrest protein expression and cellular senescence. Inhibition of progerin prenylation using a pravastatin–zoledronate combination partly prevents these defects. Our data suggest a direct proatherogenic role of progerin in human endothelial cells, which could contribute to HGPS-associated early atherosclerosis and also potentially be involved in physiological endothelial aging participating to age-related cardiometabolic diseases.

scholarly journals Involvement of Nrf2 in Ocular Diseases

2017 ◽  
Vol 2017 ◽  
pp. 1-18 ◽  
Author(s):  
Shehzad Batliwala ◽  
Christy Xavier ◽  
Yang Liu ◽  
Hongli Wu ◽  
Iok-Hou Pang
Keyword(s):  
Oxidative Stress ◽  
Diabetic Retinopathy ◽  
Macular Degeneration ◽  
Human Body ◽  
Age Related Macular Degeneration ◽  
Ocular Diseases ◽  
Checks And Balances ◽  
Age Related ◽  
The World

The human body harbors within it an intricate and delicate balance between oxidants and antioxidants. Any disruption in this checks-and-balances system can lead to harmful consequences in various organs and tissues, such as the eye. This review focuses on the effects of oxidative stress and the role of a particular antioxidant system—the Keap1-Nrf2-ARE pathway—on ocular diseases, specifically age-related macular degeneration, cataracts, diabetic retinopathy, and glaucoma. Together, they are the major causes of blindness in the world.

scholarly journals Ishige okamurae Ameliorates Methylglyoxal-Induced Nephrotoxicity via Reducing Oxidative Stress, RAGE Protein Expression, and Modulating MAPK, Nrf2/ARE Signaling Pathway in Mouse Glomerular Mesangial Cells

Foods ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2000
Author(s):  
Mingyeong Kim ◽  
Chiheung Cho ◽  
Changjun Lee ◽  
Bomi Ryu ◽  
Sera Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mesangial Cells ◽  
Apoptotic Cell ◽  
Antioxidant Response ◽  
Diabetic Complication ◽  
Related Factor ◽  
Glomerular Mesangial Cells ◽  
Ishige Okamurae ◽  
Age Related

Advanced glycation end-products (AGEs) such as methylglyoxal (MGO) play a vital role in the pathogenesis of nephropathy, a diabetic complication. In the present study, we evaluated the anti-glycation and renal protective properties of Ishige okamurae extract (IOE) against AGE-induced oxidative stress. HPLC analysis confirmed that bioactive phlorotannins such as diphlorethohydroxycarmalol and ishophloroglucin A are predominantly present in IOE. IOE showed strong anti-glycation activities via inhibition of AGE formation, inhibition of AGE–protein cross-linking, and breaking of AGE–protein cross-links. In addition, in vitro studies using mesangial cells demonstrated that IOE effectively suppressed intracellular reactive oxygen species production, intracellular MGO accumulation, and apoptotic cell death by MGO-induced oxidative stress, in addition to regulating the expression of proteins involved in the receptor for AGEs and nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response elements (ARE) signaling pathways. Therefore, IOE can serve as a natural therapeutic agent for the management of AGE-related nephropathy.

scholarly journals PEDF in Diabetic Retinopathy: A Protective Effect of Oxidative Stress

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Xiao-feng Zhu ◽  
Hai-dong Zou
Keyword(s):  
Oxidative Stress ◽  
Diabetic Retinopathy ◽  
Pigment Epithelium ◽  
Vital Role ◽  
Probable Mechanism ◽  
Multifunctional Protein ◽  
Pigment Epithelium Derived Factor ◽  
Working Age ◽  
Near Future ◽  
And Oxidative Stress

Diabetic retinopathy (DR) is a major cause of blindness in working age adults, and oxidative stress plays a vital role in the pathogenesis of DR. Pigment-epithelium-derived factor (PEDF), a multifunctional protein, has shown to inhibit the development of DR by accumulating evidence. This paper highlights the current understanding of probable mechanism about how PEDF blocks the deterioration of DR through its antioxidative properties and application prospects of PEDF as a novel therapeutic target in DR. Gene therapy of PEDF is becoming more and more acceptable and will widely be applied to the actual treatment in the near future.

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