Exp Mol Med.  2012 Feb;44(2):167-175. 10.3858/emm.2012.44.2.012.

Accumulation of argpyrimidine, a methylglyoxal-derived advanced glycation end product, increases apoptosis of lens epithelial cells both in vitro and in vivo

• Kim J
• Kim OS
• Kim CS
• Sohn E
• Jo K
• Kim JS

• KMID: 1120135
• DOI: http://doi.org/10.3858/emm.2012.44.2.012

Abstract

The formation of advanced glycation end products (AGEs) has been considered to be a potential causative factor of injury to lens epithelial cells (LECs). Damage of LECs is believed to contribute to cataract formation. The purpose of this study was to investigate the cytotoxic effect of AGEs on LECs both in vitro and in vivo. We examined the accumulation of argpyrimidine, a methylglyoxal-derived AGE, and the expression of apoptosis-related molecules including nuclear factor-kappaB (NF-kappaB), Bax, and Bcl-2 in the human LEC line HLE-B3 and in cataractous lenses of Zucker diabetic fatty (ZDF) rats, an animal model of type 2 diabetes. In cataractous lenses from twenty-one-week-old ZDF rats, LEC apoptosis was markedly increased, and the accumulation of argpyrimidine as well as subsequent activation of NF-kappaB in LECs were significantly enhanced. The ratio of Bax to Bcl-2 protein levels was also increased. In addition, the accumulation of argpyrimidine triggered apoptosis in methylglyoxal-treated HLE-B3 cells. However, the presence of pyridoxamine (an AGEs inhibitor) and pyrrolidine dithiocarbamate (a NF-kappaB inhibitor) prevented apoptosis in HLE-B3 cells through the inhibition of argpyrimidine formation and the blockage of NF-kappaB nuclear translocalization, respectively. These results suggest that the cellular accumulation of argpyrimidine in LECs is NF-kappaB-dependent and pro-apoptotic.

Keyword

apoptosis; argpyrimidine; cataract; diabetes mellitus, type 2; epithelial cells; glycosylation end products, advanced; lens, crystalline; NF-kappaB

MeSH Terms

Animals
Apoptosis/*drug effects
Cell Line
Epithelial Cells/*cytology/*drug effects
Glycosylation End Products, Advanced/*pharmacology
Lens, Crystalline/*cytology
Male
Ornithine/*analogs & derivatives/pharmacology
Pyrimidines/*pharmacology
Pyruvaldehyde/*chemistry
Rats