Du X L, Sui G Z, Stockklauser-Färber K, Weiss J, Zink S, Schwippert B, Wu Q X, Tschöpe D, Rösen P
Department of Pathophysiology of Peking Union Medical College, China.
Diabetologia. 1998 Mar;41(3):249-56. doi: 10.1007/s001250050900.
There is much evidence that diabetes and hyperglycaemia contribute to the impairment of endothelial function and induce severe changes in the proliferation, the adhesive and synthetic properties of endothelial cells. Induction of apoptosis could represent one mechanism to prevent the new accumulation of those vascular defects and to allow generation of vascular endothelium. In this study, we demonstrate that high concentrations of glucose or proinsulin induce apoptosis in human umbilical endothelial cells by three independent methods (DNA fragmentation, fluorescence activated cell sorting analysis, and morphology). The number of apoptotic cells was increased by glucose (30 mmol/l or proinsulin (100 nmol/l) from less than 10% to about 30%. Activation of protein kinase C (PKC) largely prevented the induction of apoptosis, whereas inhibition of PKC further increased the number of apoptotic cells. Similar changes as induced by glucose were also observed after incubation of the cells with the non-metabolisable 3-O-methylglucose. These findings indicate that hyperglycaemic conditions stimulate the induction of apoptosis in endothelial cells by a mechanism which is independent from the formation of diacylglycerol and the activation of PKC. The induction of apoptosis by the non-metabolisable glucose suggests that formation of oxygen derived radicals by autoxidative processes is involved and may lead to an activation of transcription factors such as nuclear transcription factor-kappaB (NF-kappaB) transferring the activation signal into the nucleus and leading to changes in gene expression necessary for induction of apoptosis.
有大量证据表明，糖尿病和高血糖会导致内皮功能受损，并引起内皮细胞增殖、黏附及合成特性的严重改变。诱导细胞凋亡可能是防止这些血管缺陷重新积累并促使血管内皮生成的一种机制。在本研究中，我们通过三种独立方法（DNA片段化、荧光激活细胞分选分析和形态学）证明，高浓度葡萄糖或胰岛素原可诱导人脐静脉内皮细胞凋亡。葡萄糖（30 mmol/L）或胰岛素原（100 nmol/L）可使凋亡细胞数量从不到10%增加至约30%。蛋白激酶C（PKC）的激活在很大程度上可防止细胞凋亡的诱导，而PKC的抑制则会进一步增加凋亡细胞数量。在用不可代谢的3 - O - 甲基葡萄糖孵育细胞后，也观察到了与葡萄糖诱导的类似变化。这些发现表明，高血糖状况通过一种独立于二酰基甘油形成和PKC激活的机制刺激内皮细胞凋亡的诱导。不可代谢葡萄糖诱导的细胞凋亡提示，自氧化过程中氧自由基的形成参与其中，并且可能导致转录因子如核转录因子 - κB（NF - κB）的激活，将激活信号传递至细胞核并导致诱导凋亡所需的基因表达发生变化。
