Effect of Cysteine on Methylglyoxal-Induced Renal Damage in Mesangial Cells

Abstract

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.

Cudrania tricuspidata Root Extract Prevents Methylglyoxal‐Induced Inflammation and Oxidative Stress via Regulation of the PKC‐NOX4 Pathway in Human Kidney Cells

“…MGO- and MGO-mediated AGEs are increased in DN patients, and they are important factors in DN progression [ 58 – 60 ]. It is well established that MGO increases oxidative stress and cell damage/death in endothelial cells [ 61 ] and several kidney cells including mesangial cells [ 62 , 63 ], podocytes [ 64 ], and tubular epithelial cells [ 26 , 27 , 65 ]. According to several studies [ 26 – 28 , 35 ], including the present study, MGO-induced oxidative stress activates MAPK/NF κ B signaling and induces an inflammatory response in renal tubular epithelial cells.…”

In Vitro Evaluation of the Toxicological Profile and Oxidative Stress of Relevant Diet‐Related Advanced Glycation End Products and Related 1,2‐Dicarbonyls

“…In recent studies, it has been found that MGO also induces ROS production in human embryonic kidney cells [ 74 ]. In SH-SY5Y cells, it was reported an increase in H 2 O 2 , O 2 •- , and • NO production after incubating with MGO, which also induced lipid peroxidation, protein carbonyls and thiols, protein nitration, and DNA oxidative damage.…”

<i>Salvia miltiorrhiza</i> Prevents Methylglyoxal-Induced Glucotoxicity <i>via</i> the Regulation of Apoptosis-Related Pathways and the Glyoxalase System in Human Umbilical Vein Endothelial Cells

“…After incubation, cells were treated with SME for 1 h, followed by 500 μM MGO treatment for 1 h. Cell lysates were prepared by using PRO-PREP™ Solution (iNtRON, Seoul, Korea; cat no. 17081), and then protein concentration were quantified using the Bradford assay protocol 5) .…”

“…When these vascular endothelial cells are exposed to certain conditions, such as hyperglycemia, insulin resistance, or mechanical stretch, cell damage is induced by apoptosis, mitogen-activated protein kinase (MAPK) signaling activation, and reaction oxygen species (ROS) overproduction, which eventually leads to endothelial dysfunction [2][3][4] . Recently, hyperglycemia-induced endothelial dysfunction has been shown to originate from dicarbonyl stress 5) . In hyperglycemia and hyperfructosemia, sugar reacts with proteins and forms a Schiff base.…”

“…In hyperglycemia and hyperfructosemia, sugar reacts with proteins and forms a Schiff base. Following this, the Amadori product undergoes a series of reactions to reactive α-dicarbonyls, and, finally, these precursors form advanced glycation end-products (AGEs) 5,6) . In a previous study, albumin, hemoglobin, fibrin, and collagen were modified to AGEs, which damaged the endothelial cells by changing the function of a protein or binding the receptor of AGEs (RAGE) 7,8) .…”