The triggering of human peritoneal mesothelial cell apoptosis and oncosis by glucose and glycoxydation products
The triggering of human peritoneal mesothelial cell apoptosis and oncosis by glucose and glycoxydation products
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DOI：
10.1093/ndt/gfh277
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发表时间：
2004-09-01
影响因子：
6.1
通讯作者：
Wautier, JL
中科院分区：
文献类型：
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作者：
Boulanger, E;Wautier, MP;Wautier, JL
背景腹膜透析液（PDF）已被证明可以改变间皮细胞功能。为了进一步确定其机制，我们研究了葡萄糖、葡萄糖降解产物（GDPs）和晚期糖基化终末产物（AGEs）对人腹膜间皮细胞（HPMC）增殖的抑制以及诱导细胞凋亡和细胞胀亡的影响。检测了四种PDF溶液，即热灭菌的蔗糖-乳酸盐、过滤的蔗糖-乳酸盐和热灭菌的蔗糖-碳酸氢盐-乳酸盐（各含15或45 g/l葡萄糖），以及热灭菌的艾考糊精-乳酸盐（含75 g/l艾考糊精）。此外，我们分析了两种葡萄糖化合物，即3-脱氧葡萄糖醛酮（3-DG），一种主要的GDP，和新的（羧甲基）-赖氨酸（CML），一种高亲和力的AGE受体（AGE）配体对HPMC活力的独立和协同作用。通过甲基-[H-3]胸苷掺入来测量细胞增殖。胀亡通过碘化丙啶（PI）DNA嵌入细胞核的能力来定量，凋亡通过线粒体跨膜电位（Am）的降低来定量。发现热灭菌的葡糖乳酸盐抑制HPMC增殖的程度大于过滤的葡萄糖-乳酸盐、热灭菌的葡糖-碳酸氢盐-乳酸盐或热灭菌的艾考糊精-乳酸盐（P < 0.00 1）。与过滤的右旋糖乳酸相比，热灭菌的右旋糖乳酸诱导的凋亡程度显著更高（P
Background. Peritoneal dialysis fluids (PDFs) have been shown to alter mesothelial cell functions. To further determine the mechanisms involved, we investigated the effects of glucose, glucose degradation products (GDPs) and advanced glycation end products (AGEs) on the inhibition of human peritoneal mesothelial cell (HPMC) proliferation and the induction of apoptosis and oncosis.Methods. Four PDF solutions, heat-sterilized dextrose-lactate, filtered dextrose-lactate and heat-sterilized dextrose-bicarbonate-lactate, each containing 15 or 45 g/l glucose, and heat-sterilized icodextrin-lactate, containing 75 g/l icodextrin, were tested. In addition, we analysed the independent and synergistic effects of two glucose compounds, i.e. 3-deoxyglucosone (3-DG), a major GDP, and New-epsilon(carboxymethyl)-lysine (CML), a high-affinity AGE receptor (RAGE) ligand on HPMC viability. Cell proliferation was measured by methyl-[H-3]thymidine incorporation. Oncosis was quantified by nuclear propidium iodide (PI) DNA-intercalating capability, and apoptosis by the decrease in mitochondrial transmembrane potential (A m).Results. It was found that heat-sterilized dextroselactate inhibited HPMC proliferation to a greater extent than filtered dextrose -lactate, heat-sterilized dextrose-bicarbonate-lactate, or heat-sterilized icodextrin-lactate (P < 0.00 1). Compared to filtered dextroselactate, heat-sterilized dextro se- lactate induced a significantly greater degree of apoptosis (P