Methylglyoxal induces cellular damage by increasing argpyrimidine accumulation and oxidative DNA damage in human lens epithelial cells.
Methylglyoxal (MGO) is a cytotoxic metabolite and modifies tissue proteins through the Maillard reaction, resulting in advanced glycation end products (AGEs), which can alter protein structure and functions. Several MGO-derived AGEs have been described, including argpyrimidine, a fluorescent product of the MGO reaction with arginine residues. Herein, we evaluated the cytotoxic role of MGO in human lens epithelial cell line (HLE-B3). HLE-B3 cells were exposed to 400 microM MGO in the present or absence of pyridoxamine for 24h. We then examined the formation of argpyrimidine, apoptosis and oxidative stress in HLE-B3 cells. In MGO-treated HLE-B3 cells, the accumulation of argpyrimidine was markedly increased, and caspase-3 and 8-hydroxydeoxyguanosine (8-OHdG) were highly expressed, which paralleled apoptotic cell death. However, pyridoxamine (AGEs inhibitor) prevented the argpyrimidine formation and apoptosis of MGO-treated HLE-B3 cells. These results suggested that the accumulation of argpyrimidine and oxidative DNA damage caused by MGO are involved in apoptosis of HLE-B3 cells.
Kim
Junghyun
J
Diabetic Complications Research Center, Division of Traditional Korean Medicine Integrated Research, Korea Institute of Oriental Medicine, Daejeon, South Korea.
Kim
Nan Hee
NH
Sohn
Eunjin
E
Kim
Chan-Sik
CS
Kim
Jin Sook
JS
D000080242:8-Hydroxy-2'-Deoxyguanosine; D017209:Apoptosis; D053148:Caspase 3 / Q000096:biosynthesis; D002460:Cell Line; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000096:biosynthesis; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D007908:Lens, Crystalline / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009952:Ornithine / Q000031:analogs & derivatives* / Q000378:metabolism; D018384:Oxidative Stress; D011733:Pyridoxamine / Q000494:pharmacology; D011743:Pyrimidines / Q000378:metabolism*; D011765:Pyruvaldehyde / Q000494:pharmacology*
D017127:Glycation End Products, Advanced; D011743:Pyrimidines; C107313:argpyrimidine; D011733:Pyridoxamine; D011765:Pyruvaldehyde; D000080242:8-Hydroxy-2'-Deoxyguanosine; D009952:Ornithine; D053148:Caspase 3; D003849:Deoxyguanosine