Skin ageing is the result of intrinsic and photo-ageing, due to UV exposure, that both share important molecular features including alterations of proteins. Indeed, proteins can be modified by many molecular processes such as glycation. Glycation occurs when glucose or its derivates the dicarbonyl compounds glyoxal (GO) and methylglyoxal (MG) react with amines of proteins leading to the formation of advanced glycation endproducts (AGE). The aim of this work is to better understand the role of glyoxalases in the detoxification of glyoxal and methylglyoxal and in the protection of keratinocyte's proteins during skin ageing. In order to understand how glyoxalases are regulated in human skin during intrinsic and photo-ageing, skin sections from 10 young and 10 old donors from photoexposed and photoprotected zones were analysed by immunohistochemistry. The glyoxalase system, glyoxalase 1 (Glo1) and glyoxalase 2 (Glo2), and AGE were localized and analysed in the skin samples. To understand the role of glyoxalases in response to dicarbonyl stress in keratinocytes, HaCaT cells were subjected to a 24h GO or MG stress and glyoxalases expression and activities were determined. Finally, proteomic studies were performed on cellular clones overexpressing Glo2 or inhibiting for Glo1 and we are currently identifying target proteins preferentially glycated by dicarbonyl compounds.Our results show that glyoxalase system is present in skin especially in the basal cells and is able to protect cellular proteins against oxidative damages. We expect that our study may contribute to decipher the role of glyoxalases in protein maintenance, which is a key element of cellular homeostasis during ageing, and to determine whether these enzymes could be targets for future anti-ageing skin strategies.
Copyright © 2014. Published by Elsevier Inc.