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Impact of Methylglyoxal and High Glucose Co-treatment on Human Mononuclear Cells
Department of Bioscience Technology and Center for Nanotechnology, Chung Yuan Christian University, Chung Li, 32023, Taiwan
* Author to whom correspondence should be addressed.
Received: 19 January 2009; in revised form: 13 March 2009 / Accepted: 26 March 2009 / Published: 31 March 2009
Abstract: Hyperglycemia and elevation of methylglyoxal (MG) are symptoms of diabetes mellitus (DM). In this report, we show that co-treatment of human mononuclear cells (HMNCs) with MG (5 μM) and high glucose (HG; 15 – 30 mM) induces apoptosis or necrosis. HG/MG co-treatment directly enhanced the reactive oxygen species (ROS) content in HMNCs, leading to decreased intracellular ATP levels, which control cell death via apoptosis or necrosis. Concentrations of 5 μM MG and 15 mM glucose significantly increased cytoplasmic free calcium and nitric oxide (NO) levels, loss of mitochondrial membrane potential (MMP), activation of caspases-9 and -3, and cell death. In contrast, no apoptotic biochemical changes were detected in HMNCs treated with 5 μM MG and 25 mM glucose, which appeared to undergo necrosis. Pretreatment with nitric oxide (NO) scavengers inhibited apoptotic biochemical changes induced by 5 μM MG/15 mM glucose, and increased the gene expression levels of p53 and p21 involved in apoptotic signaling. The results collectively suggest that the treatment dosage of MG and glucose determines the mode of cell death (apoptosis vs. necrosis) of HMNCs, and that both ROS and NO play important roles in MG/HG-induced apoptosis.
Keywords: High glucose; methylglyoxal; apoptosis; ROS; nitric oxide
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Hsieh, M.-S.; Chan, W.-H. Impact of Methylglyoxal and High Glucose Co-treatment on Human Mononuclear Cells. Int. J. Mol. Sci. 2009, 10, 1445-1464.
Hsieh M-S, Chan W-H. Impact of Methylglyoxal and High Glucose Co-treatment on Human Mononuclear Cells. International Journal of Molecular Sciences. 2009; 10(4):1445-1464.
Hsieh, Ming-Shu; Chan, Wen-Hsiung. 2009. "Impact of Methylglyoxal and High Glucose Co-treatment on Human Mononuclear Cells." Int. J. Mol. Sci. 10, no. 4: 1445-1464.