Unidad de Investigación Hospital Universitario de Getafe, Spain.
Am J Nephrol. 2011;34(2):104-14. doi: 10.1159/000329107. Epub 2011 Jun 22.
Apoptosis and inflammatory/oxidative stress have been associated with hyperglycemia in human peritoneal mesothelial cells (HPMCs) and other cell types. We and others have highlighted the role of early products of non-enzymatic protein glycation in inducing proinflammatory conditions and increasing apoptotic rates in HPMCs. Loss of HPMCs seems to be a hallmark of complications associated with peritoneal membrane dysfunction. The aim of this work is to elucidate the mechanisms by which Amadori adducts may act upon HPMC apoptosis.
HPMCs isolated from different patients were exposed to different Amadori adducts, i.e. highly glycated hemoglobin (10 nM) and glycated bovine serum albumin (250 μg/ml), to study cell death and several proapoptotic markers by different experimental approaches.
Amadori adducts, but not their respective controls, impaired cell proliferation and cell viability by means of apoptosis in a time-dependent manner. They regulated the intrinsic mitochondrial cell death signaling pathway and modulated activation of caspases, Bax, iNOS, p53, NF-κB, and mitogen-activated protein kinases (p38 and JNK) through different reactive oxygen and nitrosative species.
Our data strongly support the idea that long-term hyperglycemia could act as an inducer of apoptosis in HPMCs through Amadori adducts, involving different oxidative and nitrosative reactive species.
细胞凋亡和炎症/氧化应激与人类腹膜间皮细胞（HPMCs）和其他细胞类型的高血糖有关。我们和其他人已经强调了非酶蛋白糖基化的早期产物在诱导 HPMCs 促炎状态和增加细胞凋亡率方面的作用。HPMCs 的丢失似乎是与腹膜功能障碍相关并发症的标志。这项工作的目的是阐明 Amadori 加合物可能通过何种机制作用于 HPMC 凋亡。
从不同患者中分离出 HPMCs，使其分别暴露于不同的 Amadori 加合物，即高度糖化血红蛋白（10 nM）和糖化牛血清白蛋白（250 μg/ml），通过不同的实验方法研究细胞死亡和几种促凋亡标志物。
Amadori 加合物而非其相应对照物，以时间依赖性方式通过细胞凋亡损害细胞增殖和细胞活力。它们调节内在的线粒体细胞死亡信号通路，并通过不同的活性氧和亚硝化应激物质调节 caspase、Bax、iNOS、p53、NF-κB 和丝裂原激活蛋白激酶（p38 和 JNK）的激活。
我们的数据强烈支持这样一种观点，即长期高血糖可能通过 Amadori 加合物通过不同的活性氧和亚硝化应激物质在 HPMCs 中充当凋亡诱导剂。
