Methylglyoxal augments intracellular oxidative stress in human aortic endothelial cells

Abstract

Methylglyoxal (MGO) is a non-enzymatic metabolite in the glycolytic pathway and its concentration in blood and tissues is elevated in diabetes and renal failure. MGO induces tissue injuries via ROS; however, the mechanism remains to be clarified. The present study examined the harmful actions of MGO. Human aortic endothelial cells were assessed under real-time fluorescent microscopy with continuous superfusion. Increases in intracellular ROS were measured with fluorescent indicator, 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate acetyl ester (DCFH-DA). The addition of MGO rapidly increased the ROS in a dose-dependent manner. The increment of DCF was entirely abolished by pre-treatment with superoxide anion scavenger and membrane-permeable catalase, indicating that MGO induces superoxide production. The increment was completely inhibited by 2-thenoyltrifluoroacetone or carbonyl cyanide 3-chlorophenylhydrazone and partially inhibited by N-methyl-L-arginine. These data suggest that MGO stimulates superoxide production from mitochondria and partially stimulates nitric oxide synthase in human endothelial cells.

Methylglyoxal Is a Predictor in Type 2 Diabetic Patients of Intima-Media Thickening and Elevation of Blood Pressure

“…7,11 We reported recently that MG increases oxidative stress in vascular endothelial cells and induces vascular disorders. 4 MG indeed triggers IMT hypertrophy and PWV increase by an increase in local AGEs and oxidative stress. [1][2][3] MG is an independent risk factor of the increase of vascular stiffness (PWV) and the increase of the vascular thickness (IMT).…”

“…[1][2][3] Among toxic ␣-oxoaldehydes, the present studies were focused on methylglyoxal (MG), because the in vitro studies and animal experiments in experimental diabetic models by us and others have suggested that MG is pathologically involved in the progression of both macroangiopathy and microangiopathy: MG plays a major role in vascular damage to endothelial cells and in the development of hypertension, of insulin resistance, and of nephropathy. [1][2][3][4][5][6][7][8][9][10] The primary biosynthetic pathway of MG in diabetic patients remains elusive, but MG is known to be produced from a variety of sources. That is, MG can be produced not only from glucose but also from a variety of substances and is not necessarily produced from hyperglycemia only.…”

The effect of anti-inflammatory properties of ferritin light chain on lipopolysaccharide-induced inflammatory response in murine macrophages

“…2′,7′-Dichlorofluorescein-diacetate (DCFH-DA) is a well-established compound for detecting and quantifying intracellular ROS [18]. Intracellular ROS was measured by detecting the fluorescence intensity of DCF through the DCFH-DA-DCFH-DCF conversion as previously described [19].…”

Evolving Evidence of Methylglyoxal and Dicarbonyl Stress Related Diseases from Diabetic to Non-Diabetic Models

“…Methylglyoxal metabolism depletes intracellular GSH. Induced superoxide production also occurs in a dose dependent fashion [27]. Methylglyoxal induces cell apoptosis [28][29][30], or direct cellular toxicity with necrosis.…”