Abstract
Recently, the mechanisms responsible for anti-glycation activity of cyanidin and its derivatives on the inhibition of methylglyoxal (MG)-induced protein glycation and advanced glycation-end products (AGEs) as well as oxidative DNA damage were reported. In this study, we investigated the protective effect of cyanidin against MG-induced oxidative stress and apoptosis in rat INS-1 pancreatic β-cells. Exposure of cells to cytotoxic levels of MG (500 µM) for 12 h caused a significant reduction in cell viability. However, the pretreatment of cells with cyanidin alone (6.25–100 μM) for 12 h, or cotreatment of cells with cyanidin (3.13–100 μM) and MG, protected against cell cytotoxicity. In the cotreatment condition, cyanidin (33.3 and 100 μM) also decreased MG-induced apoptosis as determined by caspase-3 activity. Furthermore, INS-1 cells treated with MG increased the generation of reactive oxygen species (ROS) during a 6 h exposure. The MG-induced increase in ROS production was inhibited by cyanidin (33.3 and 100 μM) after 3 h stimulation. Furthermore, MG diminished the activity of glyoxalase 1 (Glo-1) and its gene expression as well as the level of total glutathione. In contrast, cyanidin reversed the inhibitory effect of MG on Glo-1 activity and glutathione levels. Interestingly, cyanidin alone was capable of increasing Glo-1 activity and glutathione levels without affecting Glo-1 mRNA expression. These findings suggest that cyanidin exerts a protective effect against MG-induced oxidative stress and apoptosis in pancreatic β-cells by increasing the activity of Glo-1.
Highlights
Methylglyoxal (MG) is a reactive dicarbonyl intermediate produced by the fragmentation of triosephosphates glyceraldehyde-3-phosphate (GAP) and dihydroxyacetone phosphate (DHAP) during glycolysis
We investigated for the first time the protective effect of cyanidin on MG-induced apoptosis in pancreatic β-cells by examining its effect on glyoxalase-1 activity and glutathione levels
Cyanidin at 33 and 100 μM concentrations reduced the proportion of early apoptotic cells about 60% and 70%, respectively, when compared to the induced apoptosis
Summary
Methylglyoxal (MG) is a reactive dicarbonyl intermediate produced by the fragmentation of triosephosphates glyceraldehyde-3-phosphate (GAP) and dihydroxyacetone phosphate (DHAP) during glycolysis. Several studies revealed that MG causes cell toxicity through oxidative stress- induced apoptosis, increased caspase activity, regulation of reactive oxygen species (ROS) scavenging enzymes, and depletion of the cellular glutathione redox status [1,2]. Nutrients 2020, 12, 1319 by inducing intracellular ROS production and oxidative damages to protein in pancreatic β-cells [4,5]. It has been shown that MG induces cytotoxicity in pancreatic INS-1 cells through activating oxidative stress and further triggering the mitochondrial apoptotic pathway and ER stress-mediated Ire1α-JNK pathway [6]. This abnormal ROS imbalance contributes to mitochondrial dysfunction that affects insulin secretion and insulin sensitivity at target tissues, leading to hyperglycemia. MG reacts with the amino acids of proteins to form chemically stable advanced glycation-end products (AGEs)
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