The hexosamine biosynthesis inhibitor azaserine prevents endothelial inflammation and dysfunction under hyperglycemic condition through antioxidant effects

Rajapakse, Angana Gupta; Ming, Xiu‐Fen; Carvas, João Miguel; Yang, Zhihong

doi:10.1152/ajpheart.00756.2008

Cited by 44 publications

(48 citation statements)

References 41 publications

(60 reference statements)

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“…The use of appropriate compounds has been described that can potentially alleviate the metabolic and functional abnormalities in diabetic retinopathy. WAS-406 (2-acetamido-1,3,6-tri-O-acetyl-2,4-dideoxy--D-xylo-hexopyranose) and Azaserine reduce cardiovascular effects caused by hyperglycemia as antioxidants rather than by inhibiting only the hexosamine pathway [123,124]. Rhein, an anthraquinone compound isolated from rhubarb, decreases hexosamine pathway and is helpful in treatment of experimental diabetic nephropathy [125].…”

Section: Inhibition Of Ros Antioxidants and Hexosamine Pathway As Ementioning

confidence: 99%

Molecular mechanisms of Diabetic Retinopathy, general preventive strategies and novel therapeutic targets

Safi¹,

Qvist²,

Kumar³

et al. 2013

Exp Clin Endocrinol Diabetes

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The growing number of people with diabetes worldwide suggests that diabetic retinopathy (DR) and diabetic macular edema (DME) will continue to be sight threatening factors. The pathogenesis of diabetic retinopathy is a widespread cause of visual impairment in the world and a range of hyperglycemia-linked pathways have been implicated in the initiation and progression of this condition. Despite understanding the polyol pathway flux, activation of protein kinase C (KPC) isoforms, increased hexosamine pathway flux, and increased advanced glycation end-product (AGE) formation, pathogenic mechanisms underlying diabetes induced vision loss are not fully understood. The purpose of this paper is to review molecular mechanisms that regulate cell survival and apoptosis of retinal cells and discuss new and exciting therapeutic targets with comparison to the old and inefficient preventive strategies. This review highlights the recent advancements in understanding hyperglycemia-induced biochemical and molecular alterations, systemic metabolic factors, and aberrant activation of signaling cascades that ultimately lead to activation of a number of transcription factors causing functional and structural damage to retinal cells. It also reviews the established interventions and emerging molecular targets to avert diabetic retinopathy and its associated risk factors.

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Section: Inhibition Of Ros Antioxidants and Hexosamine Pathway As Ementioning

confidence: 99%

Molecular mechanisms of Diabetic Retinopathy, general preventive strategies and novel therapeutic targets

Safi¹,

Qvist²,

Kumar³

et al. 2013

Exp Clin Endocrinol Diabetes

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“…Гипергликемия при СД активирует процессы окис-ления глюкозы путем пентозофосфатного цикла [10]. Этот путь метаболизма глюкозы использует каскад фер-ментов, первичным из которых является глюкозо-6-фос-фатаза.…”

Section: оксид азота (No)unclassified

“…В дальнейшем сорбитол может окисляться посредством фермента сорбитол-дегидрогеназы во фруктозу, что тре-бует избыточного участия НАДФ. Нарушение равновесия цитозольного НАДФ ингибирует фермент гликоальде-гид-3-фосфат-дегидрогеназу, что приводит к накоплению конечных продуктов окисления глюкозы [10] (см. рис.…”

Section: оксид азота (No)unclassified

Oxidative stress in pregnant women with diabetes mellitus

et al. 2018

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Oxidative stress (OS) plays an important role in embryo development, implantation, placentation, fetal development and labour. Diabetes mellitus (DM) is associated with an increase in OS processes. However, the expression of OS biomarkers in pregnant women with DM remains unclear. Based on a literature review, the features of the pro- and anti-oxidant systems of pregnant women with different types of DM have been established. Pregnancy in patients with DM has been shown to be characterised by an activation of OS processes. This leads to an overexpression of free radicals (peroxynitrite), toxic derivatives (malonic dialdehyde, 8-isoprostane) and specific enzymes (asymmetric dimethylarginine, catalase) and a decrease in the synthesis of antioxidants (superoxide dismutase, glutathione peroxidase and uric acid). The modified expression of these biomarkers is observed both in the blood and the placenta of pregnant women. These disorders can cause an unfavourable course of pregnancy, abnormal development of the placenta and development of adverse perinatal outcomes in pregnant women with DM. Nevertheless, given the inconsistency of data obtained, further scientific studies are needed to clarify this issue.

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“…Despite this, the early phases of epigenetically changes in EPCs are pre-diabetic situation affected mitochondrial injury upon hyperglycemic insult, oxidative stress activation, and lowering survival ability of cell organelles [13]. Indeed, lowered cell membrane protection against hyperglycemic endothelial damage through weak antioxidant effect and insufficient hexosamine biosynthetic pathway may independently increase oxidative stress, amplify endothelial inflammation, and impair endothelial and angiopoetic functions [14]. In this context, even transient hyperglycemia may induce long-lasting activating epigenetic changes in the promoter of the nuclear factor kappaB (NFkappaB) subunit p65 in EPCs [15].…”

Section: Editorialmentioning

confidence: 99%

Epigenetic Mechanisms of Endothelial Progenitor Cell Dysfunction

Berezin¹

2016

J Clin Epigenet

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Diabetes mellitus remains a leading factor contributing increased morbidity and mortality worldwide. The development and progression of DM associates with microvascular and macrovascular complications linked the DM with cardiovascular events. The impaired ability of endothelium to repair the injury and restore integrity depends in part on number and function of endothelial progenitor cells (EPCs). The mechanisms underlying EPC dysfunction in DM predominantly include weak bone marrow mobilization, decreased proliferation, and shortened survival. The weak function and lowered number of EPCs obtained from peripheral blood were recently found in 1 type and 2 type of DM. It has suggested that glucose toxicity, lipid toxicity, inflammation and oxidative stress may directly and indirectly via several molecular mechanisms worse of EPCs function and, however, lead to deficiency of circulating angiopoetic progenitors. Epigenetic changes are considered important key to understand whether EPCs dysfunction is reversible setting or not. The aim of editorial is to discuss around the role of epigenetic changes in EPCs in linking of DM with cardiovascular risk. Keywords: Diabetes mellitus; Endothelial progenitor cells; Endothelial dysfunction; Endothelial injury; Impaired vascular reparation; Cardiovascular risk EditorialDiabetes mellitus (DM) is a major metabolic factor leading to increased mortality and morbidity associated with higher incidence of disability, huge social and economic burden [1,2]. Recent basic and clinical studies have shown that development and progression of DM has impaired endothelium structure and integrity via several molecular mechanisms induced by glucose toxicity, lipid toxicity, oxidative stress, and inflammation [3][4][5][6]. On this way, epigenetic changes affected function and structure of endothelial-derived progenitor cells (EPCs) might lead to worsening of endothelium reparation [7]. Moreover, the EPCs dysfunction might be a clue in the initiation of DM-related microvascular and macrovascular complications [8,9] having a great predictive value [9].EPCs originated from bone marrow cells and peripheral blood cells support endothelial homoeostasis and attenuate angiogenesis. The mechanisms underlying EPC dysfunction in DM predominantly include weak bone marrow mobilization, decreased proliferation, and shortened survival [10]. Importantly, the deregulation of epigenetic features of EPCs plays a key role in DM-induced vascular injury and endothelial dysfunction [11]. DNA methylation / hydroxymethylation / transmethylation, histone modifications, and differential expression of specific non-coding RNAs like microRNA (miRNAs) are discussed as causative mechanisms of epigenetic modifications [12]. Despite this, the early phases of epigenetically changes in EPCs are pre-diabetic situation affected mitochondrial injury upon hyperglycemic insult, oxidative stress activation, and lowering survival ability of cell organelles [13]. Indeed, lowered cell membrane protection against hyperglycemic endoth...

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The hexosamine biosynthesis inhibitor azaserine prevents endothelial inflammation and dysfunction under hyperglycemic condition through antioxidant effects

Cited by 44 publications

References 41 publications

Molecular mechanisms of Diabetic Retinopathy, general preventive strategies and novel therapeutic targets

Molecular mechanisms of Diabetic Retinopathy, general preventive strategies and novel therapeutic targets

Oxidative stress in pregnant women with diabetes mellitus

Epigenetic Mechanisms of Endothelial Progenitor Cell Dysfunction

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