Glyceraldehyde May Induce the Generation of High-Molecular-Weight Species of HSP90β and Autophagy-Related Proteins and Alter Protein Levels in Human Renal Epithelial Cells

Kidney disease (KD) is a major health problem, and metabolic disorders contribute to diabetic nephropathy and chronic kidney disease, in which renal epithelial cell dysfunction plays an important role. Intracellular advanced glycation end-products (AGEs) may contribute to KD progression by disrupting cellular homeostasis; however, the underlying mechanisms remain unclear. Therefore, we aimed to investigate the effects of glyceraldehyde (GA) on molecular chaperone- and autophagy-related proteins in human renal epithelial cells (HK-2), with particular attention to AGE-related processes. Administration of high-fructose corn syrup to healthy Wistar rats increased argpyrimidine immunoreactivity in the renal tubular epithelial cells, compared with that in controls, suggesting enhanced accumulation of this GA-related AGE in vivo. In HK-2 cells, GA treatment caused concentration-dependent reductions in NADPH and ATP levels, accompanied by morphological changes. High molecular weight (HMW) immunoreactive species of HSP90β, Beclin-1, and ATG7 appeared following GA treatment. GA at 1.5 mM increased LC3-I, LC3-II, and p62 levels, whereas treatment with 2 mM GA attenuated these increases. Aminoguanidine, an inhibitor of AGE formation, attenuated these GA-induced alterations. Overall, GA may induce the generation of HMW species of HSP90β and autophagy-related proteins and may contribute to altered cellular homeostasis, with AGE-related processes potentially contributing to these effects.