Efficient in vitro lowering of carbonyl stress by the glyoxalase system in conventional glucose peritoneal dialysis fluid

Inagi, Reiko; Miyata, Toshio; Ueda, Yoshimichi; Yoshino, Atsushi; Nangaku, Masaomi; Strihou, Charles van Ypersele de; Kurokawa, Kiyoshi

doi:10.1046/j.1523-1755.2002.00488.x

Cited by 35 publications

(33 citation statements)

References 30 publications

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“…Deficiency of glyoxalase I was associated with unusually increased levels of AGEs and their precursors, implicating the involvement of the glyoxalase detoxification system, especially glyoxalase I, in the final AGE level in an uremic patient [104]. This assumption was supported in vitro by Inagi et al [105]. The glyoxalase I (GLO I) system was used as a new more physiological approach to lower RCO content in peritoneal fluids.…”

Section: Prevention Of Age Formationmentioning

confidence: 91%

Recent Concepts in the Molecular Biology of the Peritoneal Membrane – Implications for More Biocompatible Dialysis Solutions

Mortier

Vriese²,

Lameire³

2003

Blood Purif

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This paper reviews some important recent findings on the molecular biology of the peritoneal membrane. It attempts to correlate in vitro and in vivo experimental results with the possible clinical consequences. The most common functional alteration during long-term CAPD is increased peritoneal small-solute transport rate, resulting in impaired ultrafiltration and decreased dialysis efficiency. This contribution first discusses the most relevant advances in the biochemistry and molecular biology of the peritoneal membrane following peritonitis and as consequence of the continuous exposure to unphysiological dialysis fluids. In a second part the preliminary experimental and clinical experience with more biocompatible fluids is summarized. The most relevant structural and functional alterations of the membrane following repeated peritonitis is the consequence of the response of the peritoneum to infective organisms involving the inflammatory cytokines and the interaction between membrane resident cell populations: macrophages, mesothelial cells and fibroblasts. In this setting, human biopsy studies and animal experiments have identified an increase in the peritoneal-associated vasculature, which seems to be the primary cause of increased solute transport. The structural and functional alterations in the membrane in long-term peritoneal dialysis are thought to be the consequence of the toxicity of glucose, either directly or indirectly through the generation of glucose degradation products or the formation of advanced glycation end-products. In particular, an important role for vascular endothelial growth factor and nitric oxide as downstream mediators of the alterations has been suggested. Finally, the last part of this paper reviews the actual and future research aimed at an amelioration of the biocompatibility of the dialysis fluids. Replacing glucose by other osmotic agents, changing the sterilization process, replacing the lactate buffer by bicarbonate, blocking the formation of reactive carbonyl products and of the neoangiogenesis are the most promising changes to enhance the biocompatibility. Finally, gene therapy may in the future have an important contribution. Ex vivo gene therapy involves harvesting peritoneum samples to isolate mesothelial cells that will be genetically modified before re-implantation into the peritoneal cavity.

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Section: Prevention Of Age Formationmentioning

confidence: 91%

Recent Concepts in the Molecular Biology of the Peritoneal Membrane – Implications for More Biocompatible Dialysis Solutions

Mortier

Vriese²,

Lameire³

2003

Blood Purif

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“…The GLO-I transgene, isolated by digestion of pBsCAG-2 containing GLO-I cDNA with KpnI and SacI, was microinjected into one pronucleus of fertilized Wistar eggs followed by transfer into the oviducts of pseudopregnant rats. The procedure used was comparable with the generation of glyoxalase-I-overexpressing mice (14). Rat genomic DNA extracted from tail tissue was used to detect the transgene by PCR using specific primers for GLO-I or pBsCAG-2 vector.…”

Section: Methodsmentioning

confidence: 99%

Overexpression of Glyoxalase-I Reduces Hyperglycemia-induced Levels of Advanced Glycation End Products and Oxidative Stress in Diabetic Rats

Brouwers

Niessen

Ferreira

et al. 2011

Journal of Biological Chemistry

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195

137

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The reactive advanced glycation end product (AGE) precursor methylglyoxal (MGO) and MGO-derived AGEs are associated with diabetic vascular complications and also with an increase in oxidative stress. Glyoxalase-I (GLO-I) transgenic rats were used to explore whether overexpression of this MGO detoxifying enzyme reduces levels of AGEs and oxidative stress in a rat model of diabetes. Rats were made diabetic with streptozotocin, and after 12 weeks, plasma and multiple tissues were isolated for analysis of AGEs, carbonyl stress, and oxidative stress. GLO-I activity was significantly elevated in multiple tissues of all transgenic rats compared with wild-type (WT) littermates. Streptozotocin treatment resulted in a 5-fold increase in blood glucose concentrations irrespective of GLO-I overexpression. Levels of MGO, glyoxal, 3-deoxyglucosone, AGEs, and oxidative stress markers nitrotyrosine, malondialdehyde, and F2-isoprostane were elevated in the diabetic WT rats. In diabetic GLO-I rats, glyoxal and MGO composite scores were significantly decreased by 81%, and plasma AGEs and oxidative stress markers scores were significantly decreased by ϳ50%. Hyperglycemia induced a decrease in protein levels of the mitochondrial oxidative phosphorylation complex in the gastrocnemius muscle, which was accompanied by an increase in the lipid peroxidation product 4-hydroxy-2-nonenal, and this was counteracted by GLO-I overexpression. This study shows for the first time in an in vivo model of diabetes that GLO-I overexpression reduces hyperglycemia-induced levels of carbonyl stress, AGEs, and oxidative stress. The reduction of oxidative stress by GLO-I overexpression directly demonstrates the link between glycation and oxidative stress.Prolonged exposure to hyperglycemia has detrimental effects on various cellular functions and is believed to be the most important factor in the development of vascular complications in diabetes. One of the hypotheses about how hyperglycemia leads to complications is the formation of advanced glycation end products (AGEs) 3 (1). In addition to the formation of AGEs by the classical Maillard reaction (2, 3), dicarbonyls such as methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucocone (3-DG) are also known to form AGEs. MGO is probably the most important precursor in this formation of AGEs (4). This highly reactive oxo-aldehyde is formed mainly by the non-enzymatic and enzymatic fragmentation of the triose phosphates glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. MGO reacts primarily with arginine residues to form the major AGEs, hydroimidazolone (MG-H1), argpyrimidine (AP) and tetrahydropyrimidine (THP), and with lysine residues to minor AGEs such as N⑀-(1-carboxyethyl)lysine (CEL). MGO is efficiently detoxified by the glyoxalase system. In this pathway MGO reacts with reduced glutathione (GSH) to a hemithioacetal adduct and then to S-Dlactoyl-glutathione, which is catalyzed by glyoxalase-I (GLO-I). This product is converted into D-lactate by glyoxalase-II, thereby reforming the consumed GSH. A s...

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“…The levels of three reactive carbonyl compounds (RCO)-glyoxal (GO), methylglyoxal (MGO), and 3-deoxyglucosone (3-DG)-in cell culture supernatant were measured by reverse-phase HPLC as described previously (16).…”

Section: Measurement Of Reactive Carbonyl Compoundsmentioning

confidence: 99%

High Glucose Blunts Vascular Endothelial Growth Factor Response to Hypoxia via the Oxidative Stress-Regulated Hypoxia-Inducible Factor/Hypoxia-Responsible Element Pathway

Katavetin

Miyata

Inagi

et al. 2006

Journal of the American Society of Nephrology

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117

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5 cells for VEGF protein; P < 0.05 both) but not by high L-glucose. It is interesting that hydrogen peroxide also blunted this response, whereas ␣-tocopherol restored the VEGF response to hypoxia in the presence of high D-glucose. For determination of involvement of the hypoxia-inducible factor (HIF)/hypoxia-responsible element (HRE) pathway, IRPTC that were stably transfected with HREluciferase were cultured under the previous conditions. High D-glucose also reduced luciferase activity under hypoxia, whereas ␣-tocopherol restored activity. In vivo experiments using streptozotocin-induced diabetic rats confirmed that hyperglycemia blunted HIF-HRE pathway activation. Insulin treatment restored activation of the HIF-HRE pathway in streptozotocin-induced diabetic rats. In conclusion, high glucose blunts VEGF response to hypoxia in IRPTC. This effect is mediated by the oxidative stress-regulated HIF-HRE pathway.

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Efficient in vitro lowering of carbonyl stress by the glyoxalase system in conventional glucose peritoneal dialysis fluid

Cited by 35 publications

References 30 publications

Recent Concepts in the Molecular Biology of the Peritoneal Membrane – Implications for More Biocompatible Dialysis Solutions

Recent Concepts in the Molecular Biology of the Peritoneal Membrane – Implications for More Biocompatible Dialysis Solutions

Overexpression of Glyoxalase-I Reduces Hyperglycemia-induced Levels of Advanced Glycation End Products and Oxidative Stress in Diabetic Rats

High Glucose Blunts Vascular Endothelial Growth Factor Response to Hypoxia via the Oxidative Stress-Regulated Hypoxia-Inducible Factor/Hypoxia-Responsible Element Pathway

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