Effect of Cysteine on Methylglyoxal-Induced Renal Damage in Mesangial Cells.
Methylglyoxal (MGO), a highly reactive dicarbonyl compound, is a key precursor of the formation of advanced glycation end products (AGEs). MGO and MGO-AGEs were reportedly increased in patients with diabetic dysfunction, including diabetic nephropathy. The activation of glyoxalase-I (GLO-I) increases MGO and MGO-AGE detoxification. MGO-mediated glucotoxicity can also be ameliorated by MGO scavengers such as N-acetylcysteine (NAC), aminoguanidine (AG), and metformin. In this study, we noted that l-cysteine demonstrated protective effects against MGO-induced glucotoxicity in renal mesangial cells. l-cysteine prevented MGO-induced apoptosis and necrosis, together with a reduction of reactive oxygen species (ROS) production in MES13 cells. Interestingly, l-cysteine significantly reduced MGO-AGE formation and also acted as an MGO-AGE crosslink breaker. Furthermore, l-cysteine treatment accelerated MGO catabolism to D-lactate via the upregulation of GLO-I. The reduction of AGE formation and induction of AGE breakdown, following l-cysteine treatment, further supports the potential use of l-cysteine as an alternative for the therapeutic control of MGO-induced renal complications in diabetes, especially against diabetic nephropathy.
['Lee|Jae Hyuk|JH|0000-0002-4304-0198', 'Subedi|Lalita|L|', 'Kim|Sun Yeou|SY|0000-0001-8044-5613']
D000111:Acetylcysteine D000818:Animals D017209:Apoptosis D002460:Cell Line D002470:Cell Survival D003545:Cysteine D006146:Guanidines D006801:Humans D007770:L-Lactate Dehydrogenase D019344:Lactic Acid D007791:Lactoylglutathione Lyase D020935:MAP Kinase Signaling System D050527:Mesangial Cells D051379:Mice D011765:Pyruvaldehyde D017382:Reactive Oxygen Species D056564:Sirtuin 1
methylglyoxal advanced glycation end products diabetic nephropathy glyoxalase-I l-cysteine