Glyoxalase-1 overexpression reduces endothelial dysfunction and attenuates early renal impairment in a rat model of diabetes.

Brouwers O, Niessen PM, Miyata T, Ostergaard JA, Flyvbjerg A, Peutz-Kootstra CJ, Sieber J, Mundel PH, Brownlee M, Janssen BJ, De Mey JG, Stehouwer CD, Schalkwijk CG.
Journal   Diabetologia
Species  
Analytes Measured   Albumin , HAVCR1 KIM-1 , MCP-1 , Osteopontin
Matrix Tested   Cell culture supernatants, urine
Year   2014
Volume   57
Page Numbers   224-235
Application   Cytokines and Chemokines , Toxicology
Abstract
AIMS/HYPOTHESIS: In diabetes, advanced glycation end-products (AGEs) and the AGE precursor methylglyoxal (MGO) are associated with endothelial dysfunction and the development of microvascular complications. In this study we used a rat model of diabetes, in which rats transgenically overexpressed the MGO-detoxifying enzyme glyoxalase-I (GLO-I), to determine the impact of intracellular glycation on vascular function and the development of early renal changes in diabetes. RESULTS: Diabetes-induced formation of AGEs in mesenteric arteries and endothelial dysfunction were reduced by Glo1 overexpression. Despite the absence of advanced nephrotic lesions, early markers of renal dysfunction (i.e. increased glomerular volume, decreased podocyte number and diabetes-induced elevation of urinary markers albumin, osteopontin, kidney-inflammation-molecule-1 and nephrin) were attenuated by Glo1 overexpression. In line with this, downregulation of Glo1 in cultured endothelial cells resulted in increased expression of inflammation and endothelium dysfunction markers. In fully differentiated cultured podocytes incubation with MGO resulted in apoptosis.

CONCLUSIONS/INTERPRETATION: This study shows that effective regulation of the GLO-I enzyme is important in the prevention of vascular intracellular glycation, endothelial dysfunction and early renal impairment in experimental diabetes. Modulating the GLO-I pathway therefore may provide a novel approach to prevent vascular complications in diabetes.

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Eotaxin, Eotaxin-3, GM-CSF, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-8 (HA), IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC, TNF-α, TNF-β, VEGF-A | Human
Multiplex
V-PLEX Human MCP-1 Kit
MCP-1 | Human
Singleplex
V-PLEX Plus Chemokine Panel 1 Human Kit
Eotaxin, Eotaxin-3, IL-8, IL-8 (HA), IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC | Human
Multiplex
V-PLEX Plus Human Cytokine 30-Plex Kit
Eotaxin, Eotaxin-3, GM-CSF, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-8 (HA), IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC, TNF-α, TNF-β, VEGF-A | Human
Multiplex
V-PLEX Plus Human MCP-1 Kit
MCP-1 | Human
Singleplex
Chemokine Panel 1 Human Control Pack
Eotaxin, Eotaxin-3, IL-8, IP-10, MCP-1, MCP-4, MDC, TARC | Human
Inflammation Panel 3 (cyno) Kit
MCP-1, NGAL/LCN2, TIMP-1 | Non-human primate
Multiplex
Kidney Injury Panel 5 Human Kit
Albumin, B2M, Cystatin C, EGF, NGAL/LCN2, Osteopontin, Uromodulin | Human
Multiplex
Kidney Injury Panel 3 Human Kit
α-GST, Calbindin, Clusterin, HAVCR1/KIM-1, Osteoactivin, TFF3, VEGF-A | Human
Multiplex
Human KIM-1 Kit
HAVCR1/KIM-1 | Human
Singleplex
Inflammation Panel 1 Rat Kit
MCP-1, NGAL/LCN2, TIMP-1, TSP-1 | Rat
Multiplex
Rat TIM-1/KIM-1/HAVCR Kit
HAVCR1/KIM-1 | Rat
Singleplex
Mouse MCP-1 Tissue Culture Kit
MCP-1 | Mouse
Singleplex
Mouse MCP-1 Ultra-Sensitive Kit
MCP-1 | Mouse
Singleplex
Rat MCP-1 Ultra-Sensitive Kit
MCP-1 | Rat
Singleplex
V-PLEX Mouse Cytokine 29-Plex Kit
IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12p70, IL-15, IL-16, IL-17A, IL-17A/F, IL-17C, IL-17E/IL-25, IL-17F, IL-21, IL-22, IL-23, IL-27p28/IL-30, IL-31, IL-33, IP-10, KC/GRO, MCP-1, MIP-1α, MIP-2, MIP-3α, TNF-α | Mouse
Multiplex
U-PLEX Biomarker Group 1 NHP Assays
CTACK, ENA-78, Eotaxin, Eotaxin-2, Eotaxin-3, FLT3L, Fractalkine, G-CSF, GM-CSF, GRO-α, I-309, IFN-α2a, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-2Rα, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17B, IL-17C, IL-17D, IL-17F, IL-18, IL-22, IL-23, IP-10, I-TAC, MCP-1, MCP-2, MCP-3, MCP-4, M-CSF, MDC, MIF, MIP-1α, MIP-1β, MIP-3α, MIP-3β, MIP-5, SDF-1α, TARC, TGF-β1, TGF-β2, TGF-β3, TNF-α, TNF-β, TPO, TRAIL, VEGF-A, YKL-40 | Non-human primate
Multiplex
Mouse MCP-1 Antibody
MCP-1 | Mouse
V-PLEX Plus Mouse Cytokine 29-Plex Kit
IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12p70, IL-15, IL-16, IL-17A, IL-17A/F, IL-17C, IL-17E/IL-25, IL-17F, IL-21, IL-22, IL-23, IL-27p28/IL-30, IL-31, IL-33, IP-10, KC/GRO, MCP-1, MIP-1α, MIP-2, MIP-3α, TNF-α | Mouse
Multiplex
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