Methylglyoxal

About: Methylglyoxal is a research topic. Over the lifetime, 2844 publications have been published within this topic receiving 102037 citations. The topic is also known as: acetylformaldehyde & pyruvaldehyde.

Evaluation of glyoxal and methylglyoxal levels in uremic patients under peritoneal dialysis.

Abstract: Advanced glycation end products (AGEs) accumulate in serum and tissues of patients with chronic renal failure, even in the absence of diabetes, and a different clearance of these species has been observed by hemodialysis and peritoneal dialysis (CAPD). Furthermore, it has been shown that not only AGE but also 1,2-dicarbonyl compounds are formed during heat sterilization of glucose-based peritoneal dialysis fluids. Therefore, we investigated the level of some AGEs (pentosidine and free pentosidine) and dicarbonyl compounds (glyoxal and methylglyoxal) in end-stage renal disease patients subjected to peritoneal dialysis. Samples (20 from healthy subjects, 16 from uremic patients before and after 12 h of peritoneal dialysis) were analyzed, and the plasma and dialysate levels of glyoxal, methylglyoxal, pentosidine, and free pentosidine were determined. In plasma of uremic patients, mean values of pentosidine showed a small decrease after dialysis and were always higher than those of healthy control subjects. An analogous trend was observed for free pentosidine. In the case of peritoneal dialysate, no pentosidine and free pentosidine were found at time zero, whereas both compounds were detected after 12 h of dialysis. Glyoxal and methylglyoxal mean levels showed a decrease in plasma after dialysis even if their values were always higher than those of healthy control subjects. Surprisingly, an analogous trend was observed also in dialysate. These results might indicate that glyoxal and methylglyoxal already present in the dialysis fluid react with the peritoneal matrix proteins, accounting for the gradual loss of peritoneal membrane function that is often observed in patients subjected to CAPD for a long time.

Differential Susceptibility of Naive and Differentiated PC-12 Cells to Methylglyoxal-Induced Apoptosis: Influence of Cellular Redox

Abstract: Neuropathologies have been associated with neuronal de-differentiation and oxidative susceptibility. To address whether cellular states determines their oxidative vulnerability, we have challenged naive (undifferentiated) and nerve growth factor-induced differentiated pheochromocytoma (PC12) with methylglyoxal (MG), a model of carbonyl stress. MG dose-dependently induced greater apoptosis (24h) in naive (nPC12) than differentiated (dPC12) cells. This enhanced nPC12 susceptibility was correlated with a high basal oxidized cellular glutathione-to-glutathione disulfide (GSH / GSSG) redox and an MG-induced GSH-to-Disulfide (GSSG plus protein-bound SSG) imbalance. The loss of redox balance occurred at 30 min post-MG exposure, and was prevented by N-acetylcysteine (NAC) that was unrelated to de novo GSH synthesis. NAC was ineffective when added at 1h post-MG, consistent with an early window of redox signaling. This redox shift was kinetically linked to decreased BcL-2, increased Bax, and release of mitochondrial cytochrome c which preceded caspase-9 and -3 activation and poly ADP-ribose polymerase (PARP) cleavage (1-2h), consistent with mitochondrial apoptotic signaling. The blockade of apoptosis by cyclosporine A supported an involvement of the mitochondrial permeability transition pore. The enhanced vulnerability of nPC12 cells to MG and its relationship to cellular redox shifts will have important implications for understanding differential oxidative vulnerability in various cell types and their transition states.

Endogenous alpha-oxoaldehydes and formation of protein and nucleotide advanced glycation endproducts in tissue damage.

Abstract: Human and other biological tissues face a continual threat of damage by alpha-oxoaldehydes formed endogenously. Glyoxal, methylglyoxal and 3-deoxyglucosone are formed by the degradation of glycolytic intermediates, glycated proteins and lipid peroxidation. They are potent glycating agents of protein and nucleotides leading to the formation of advanced glycation endproducts (AGEs). With proteins, they are arginine residue-directed glycating agents forming mainly hydroimidazolones, found at 0.1-1% of total arginine residues in tissues (2-20% of proteins modified). With nucleotides, imidazopurinone- and N2-carboxyalkyl- derivatives of deoxyguanosine are formed, found at 0.1-0.8 per 10(6) nucleotides in DNA. Glycation occurs in all tissues and body fluids. Cellular proteolysis of AGE-modified proteins and DNA releases glycated amino acids and nucleosides. Glycated amino acids and nucleosides are released into plasma, undergo glomerular filtration and are excreted in urine. The damage to tissue protein and nucleotides by alpha-oxoaldehydes is suppressed by the metabolism of alpha-oxoaldehyde glycating agents by the glutathione-dependent enzyme, glyoxalase I, and aldo-keto reductases. These enzymatic activities are part of the enzymatic defence against glycation. Tissue damage by alpha-oxoaldehyde glycation is implicated in diabetic and non-diabetic vascular disease, renal failure, cirrhosis, Alzheimer's disease, arthritis and ageing.