Glycated albumin induces superoxide generation in mesangial cells

Background/Aims: Reactive oxygen species are involved in the pathogenesis of diabetic nephropathy. Amadori-modified glycated albumin modulates signaling pathways in mesangial cells that contribute to the development of diabetic nephropathy. However, the effects of glycated albumin on mesangial cell superoxide (O-2(-)) production are unknown. Thus, we examined whether glycated albumin induces mesangial cell O-2(-) generation and whether increased O-2(-) production elicits cell growth. Methods: Quiescent human mesangial cells (H MC) were exposed to bovine serum albumin (BSA) or glycated BSA (Gly-BSA) with or without diphenylene iodonium (DPI) or apocynin, inhibitors of NAD(P)H oxidase, GF109203X (GFX), a protein kinase C (PKC) inhibitor. Results: Gly-BSA increased PKC activity, particularly PKC-alpha and -ss1, within 15 min of incubation with HMC, which decreased to the control value at 2 h. Gly-BSA incubated with HMC increased O-2(-) production by 2 times vis-a-vis BSA-treated cells. The Gly-BSA-induced increased O-2(-) generation was suppressed by DPI or GFX Gly-BSA significantly increased mesangial [H-3]-leucine incorporation, whereas these processes were abrogated by DPI, apocynin or GFX Conclusions: Gly-BSA induces PKC/NAD(P)H oxidase-dependent O-2(-) production in HMC, which in turn results in cell hypertrophy. Thus, O-2(-) induced by glycated albumin might cause mesangial cell alterations in diabetes participating in the pathophysiology of diabetic nephropathy. Copyright (C) 2004 S. Karger AG, Basel.