Regulation of Cellular Activity by Reactive Oxygen

我们研究了被认为与衰老和糖尿病有关的糖基化反应。重点考察了其早期反应产物对抗氧化酶的影响。结果，暴露于还原糖（如果糖）的细胞发生凋亡。另一方面，糖基化反应的中间体3-脱氧葡萄糖酮和甲基乙二醛等毒性很强的化合物可诱导某些细胞凋亡。建立了一种针对果糖-蛋白质中间产物（果糖赖氨酸）的抗体。我们证实了晶体蛋白在多元醇代谢途径活跃的大鼠晶状体中聚结。此外，我们还研究了糖基化中间体诱导肝素结合的表皮生长因子样生长因子（HB-EGF）与平滑肌细胞生长的关系。甲基乙二醛和3-脱氧葡萄糖酮诱导平滑肌细胞HB-EGF表达。虽然这些中间体增加了细胞内过氧化物，但抗氧化剂n -乙酰半胱氨酸却抑制了基因的表达。这些数据提示活性氧以某种方式参与HB-EGF基因的表达。

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.