RAGE and glyoxalase in kidney disease.
Glycation is an important reaction in the regulation of physiological state. When poorly controlled, however, glycation can also result in the accumulation of glycated proteins (advanced glycation endproducts; AGEs) in the body. This AGE accumulation is termed glycative stress, and is an established pathological factor: to date, glycative stress has been closely associated with not only kidney diseases, but also kidney aging. Accumulating evidence demonstrates that the progression of renal tubular damage and tubular aging are often correlated with activation of the receptor for the AGE (RAGE)-AGE pathway or decreased activity of glyoxalase 1, which is an anti-glycation enzyme to lower glycative stress. Further, glycative stress exacerbates the derangement of protein homeostasis: the posttranslationally modified proteins by glycation often lose or gain their functions. Such deranged protein homeostasis leads to endoplasmic reticulum (ER) stress, a state of ER dysfunction in which the quality control of proteins is defective, as well as to induction of its stress signal, the unfolded protein response (UPR), in the kidney. The lowering of glycative stress via modulation of RAGE-AGE axis or glyoxalase 1 activity is beneficial for tubular homeostasis and the subsequent prevention and treatment of kidney disease, suggesting the possibility of novel therapeutic approaches which target glycative stress. In this review, we focused on the impact of glycative stress in the kidney, especially the role of RAGE and glyoxalase 1. Further we also discuss the crosstalk between glycative stress and ER stress in their effect on protein homeostasis.
Division of Chronic Kidney Disease (CKD) Pathophysiology, The University of Tokyo Graduate School of Medicine, 7-3-1, Hongo Bunkyo-ku, Tokyo, 113-8655, Japan. inagi-npr@umin.ac.jp.
Reiko
R
Inagi
D059865:Endoplasmic Reticulum Stress; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D007791:Lactoylglutathione Lyase / Q000378:metabolism*; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism*; D056811:Unfolded Protein Response
C000593871:AGER protein, human; D000067759:Receptor for Advanced Glycation End Products; C000597196:GLO1 protein, human; D007791:Lactoylglutathione Lyase
Diabetic nephropathy; Endoplasmic reticulum (ER) stress; Epigenetics; Glycative stress; Kidney aging; Oxidative stress