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

Jae Hyuk Lee,Lalita Subedi,Sun Yeou Kim

doi:10.3390/cells9010234

Jae Hyuk Lee, Lalita Subedi + Show 1 more

Open Access

https://doi.org/10.3390/cells9010234

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Journal: Cells	Publication Date: Jan 17, 2020
Citations: 12	License type: CC BY 4.0

Affiliation: Gachon University, Gachon University Gil Medical Center

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.

Highlights

Methylglyoxal (MGO) is a dicarbonyl compound produced by the degradation of carbohydrates [1].Hyperglycemia with diabetic complications is the main cause of the excessive accumulation of MGO in the body [2,3]
Our results significantly increase the breakdown of MGO-advanced glycation end products (AGEs) in a dose-dependent manner (Figures 4D and showedS2D)
We investigated the change of cytoskeletal protein by immunofluorescence analysis (IF) and confocal microscope

Summary

Introduction

Hyperglycemia with diabetic complications is the main cause of the excessive accumulation of MGO in the body [2,3]. Cardiovascular and chronic kidney diseases (CKD) are considered as the major complications in diabetic patients that have been caused by MGO/MGO-AGEs [5,6]. Increased MGO levels in diabetic patients are believed to contribute to vascular dysfunction and renal impairment [6]. There are increasing reports suggesting that chronic renal disease can be caused by excessive MGO accumulation and MGO-glyoxalase system inactivation [7,8,9]. A previous study reported that higher MGO plasma levels were linked with disturbed glomerular filtration rates and diabetic chronic kidney disease [8]

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