Effects of zinc and manganese on advanced glycation end products (AGEs) formation and AGEs-mediated endothelial cell dysfunction

Zhuang, Xiuyuan; Pang, Xiufeng; Wen, Zhang; Wu, Wenbin; Zhao, Jingjing; Yang, Huang-jian; Qu, Wei

doi:10.1016/j.lfs.2011.10.025

Cited by 33 publications

(29 citation statements)

References 32 publications

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“…AGEs was able to reduce NO production and eNOS expression under the condition of high glucose [5]. AGEs also increases ROS production by activation of NADPH oxidase [7, 8]. AGE inhibitor, aminoguanidine, can improve endothelial function in diabetic animal models [1, 4].…”

Section: Introductionmentioning

confidence: 99%

Advanced glycation end-products decreases expression of endothelial nitric oxide synthase through oxidative stress in human coronary artery endothelial cells

Ren

Qin

et al. 2017

Cardiovasc Diabetol

117

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BackgroundAdvanced glycation end-products (AGEs) are elevated under diabetic conditions and associated with insulin resistance, endothelial dysfunction and vascular inflammation in humans. It has been demonstrated that AGEs evoke oxidative and inflammatory reactions in endothelial cells through the interaction with a receptor for AGEs (RAGE). Here, we aimed to identify the cellular mechanisms by which AGEs exacerbate the endothelial dysfunction in human coronary artery endothelial cells (HCAECs).Methods30 type 2 diabetic patients with or without coronary artery atherosclerosis were recruited for this study. Plasma levels of AGE peptides (AGE-p) were analyzed using flow injection assay. Endothelial function was tested by brachial artery flow-mediated vasodilatation (FMD). Further investigations were performed to determine the effects and mechanisms of AGEs on endothelial dysfunction in HCAECs.ResultsAGE-p was inversely associated with FMD in diabetic patients with coronary artery atherosclerosis in our study. After treated with AGEs, HCAECs showed significant reductions of eNOS mRNA and protein levels including eNOS and phospho-eNOS Ser1177, eNOS mRNA stability, eNOS enzyme activity, and cellular nitric oxide (NO) levels, whereas superoxide anion production was significantly increased. In addition, AGEs significantly decreased mitochondrial membrane potential, ATP content and catalase and superoxyde dismutase (SOD) activities, whereas it increased NADPH oxidase activity. Treatment of the cells with antioxidants SeMet, SOD mimetic MnTBAP and mitochondrial inhibitor thenoyltrifluoroacetone (TTFA) effectively blocked these effects induced by AGEs. AGEs also increased phosphorylation of the mitogen-activated protein kinases p38 and ERK1/2, whereas the specific inhibitors of p38, ERK1/2, and TTFA effectively blocked AGEs-induced reactive oxygen species production and eNOS downregulation.ConclusionsAGEs cause endothelial dysfunction by a mechanism associated with decreased eNOS expression and increased oxidative stress in HCAECs through activation of p38 and ERK1/2.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-017-0531-9) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Advanced glycation end-products decreases expression of endothelial nitric oxide synthase through oxidative stress in human coronary artery endothelial cells

Ren

Qin

et al. 2017

Cardiovasc Diabetol

117

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“…A common indication of endothelial cell dysfunction is enhanced oxidation, and AGEs have been associated with this (22). Therefore, the present study investigated the concentrations of MDA and NO, and the activities of SOD, GSH-Px and eNOS to further confirm the protective effects of physiological testosterone on AGE-induced injury in HUVECs.…”

Section: Resultsmentioning

confidence: 99%

Protective effects of physiological testosterone on advanced glycation end product-induced injury in human endothelial cells

Xie¹,

et al. 2017

Molecular Medicine Reports

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The effect of testosterone, a sex steroid, on endothelial cells is controversial as it is uncertain if it has a protective effect on them. Whether physiological testosterone can inhibit the deleterious effects of advanced glycation end products (AGEs) on endothelial cells remains to be elucidated. The present study focused on elucidating the effect of testosterone on the injury of endothelial cells induced by AGEs. Human umbilical vein endothelial cells (HUVECs) were cultured in vitro and treated with AGEs in the presence or absence of various concentrations of testosterone. The cell viability in each group was measured using an MTS assay. Early-stage apoptosis was detected using flow cytometry with Annexin V-fluorescein isothiocyanate/propidium iodide double staining, and the expression levels of apoptosis-associated proteins, B cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax) and caspase-3, were determined using western blot analysis. Oxidative stress and pro-inflammatory parameters in the medium were evaluated using an enzyme-linked immunosorbent assay. The MTS results showed that AGEs significantly decreased the proliferation of HUVECs, whereas a physiological concentration of testosterone alleviated this damage. Physiological concentrations of testosterone protected the HUVECs from AGE-induced apoptosis, mediated by caspase-3 and Bax/Bcl-2. In addition, treatment of the HUVECs with AGEs caused a significant decrease in anti-oxidative parameters, but increased the concentrations of malondialdehyde and tumor necrosis factor-α. The activation of Janus kinase 2 and signal transducer and activator of transcription 3 was significantly increased by incubation with AGEs. However, pre-incubation with a physiological concentration of testosterone attenuated these changes. Therefore, the data obtained in the present study established the potential role of physiological testosterone in ameliorating AGE-induced damage in HUVECs.

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“…Glycation is the result of a condensation reaction, also termed Maillard reaction, between free protein amine groups and a reducing sugar, resulting in unstable Schiff bases 73 . Subsequent spontaneous oxidation or rearrangement leads to the more stable Amadori products, which are eventually transformed through a series of intermediates into advanced glycation end products (AGE) 74 . Even though one has not observed a specific sequence of the positively charged primary amines located on the protein structure's surface, which increases the likelyhood of glycation, local environments that contain histidine residues or basic residues seem to favor glycation in structurally known proteins 75 .…”

Section: Glycosylationmentioning

confidence: 99%

“…In addition, it has been described that Cu 2+ and Fe 3+ play major roles in the generation of glycation products 73 . Another study recognized the excellent inhibitory effect of Mn 2+ (5-20 µM) and the stimulating effect of Zn 2+ (5-20 µM) on advanced glycation end products formation (AGE) 74 . In an animal study, rats accumulated AGE in various tissues due to fructose intake 145 .…”

Section: Glycationmentioning

confidence: 99%

Tailoring recombinant protein quality by rational media design

Brühlmann

Jordan

Hemberger³

et al. 2015

Biotechnology Progress

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Clinical efficacy and safety of recombinant proteins are closely associated with their structural characteristics. The major quality attributes comprise glycosylation, charge variants (oxidation, deamidation, and C‐ & N‐terminal modifications), aggregates, low‐molecular‐weight species (LMW), and misincorporation of amino acids in the protein backbone. Cell culture media design has a great potential to modulate these quality attributes due to the vital role of medium in mammalian cell culture. The purpose of this review is to provide an overview of the way both classical cell culture medium components and novel supplements affect the quality attributes of recombinant therapeutic proteins expressed in mammalian hosts, allowing rational and high‐throughput optimization of mammalian cell culture media. A selection of specific and/or potent inhibitors and activators of oligosaccharide processing as well as components affecting multiple quality attributes are presented. Extensive research efforts in this field show the feasibility of quality engineering through media design, allowing to significantly modulate the protein function. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 31:615–629, 2015

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Effects of zinc and manganese on advanced glycation end products (AGEs) formation and AGEs-mediated endothelial cell dysfunction

Cited by 33 publications

References 32 publications

Advanced glycation end-products decreases expression of endothelial nitric oxide synthase through oxidative stress in human coronary artery endothelial cells

Advanced glycation end-products decreases expression of endothelial nitric oxide synthase through oxidative stress in human coronary artery endothelial cells

Protective effects of physiological testosterone on advanced glycation end product-induced injury in human endothelial cells

Tailoring recombinant protein quality by rational media design

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