Regulation of Cellular Activity by Reactive Oxygen

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We have investigated the glycation reaction which is assumed to be involved in aging and diabetes mellitus. Especially, effects of its early reaction products on antioxidative enzymes were examined. As results, cells exposed to reducing sugars such as fructose underwent apoptosis. On the other hand, 3-deoxyglucosone and methylglyoxal, reaction intermediates of the glycation reaction and very toxic compounds, were found to induce apoptosis in certain cells. An antibody was raised against fructated intermediary product of proteins with fructose (fructated lysine). We confirmed that crystallins were fructated in rat lens where the polyol metabolic pathway is active. In addition, we examined relationship between mechanism of induction of heparin-binding epidermal growth factor-like growth factor (HB-EGF) by glycation intermediates and growth of smooth muscle cells. Methylglyoxal and 3-deoxyglucosone induced HB-EGF expression in smooth muscle cells. While these intermediate increased the intracellular peroxides, N-acetylcysteine, an antioxidant, rather suppressed the gene expression. These data suggest that reactive oxygen species are somehow involved in the expression of HB-EGF gene.