Hung Kuan-Yu, Liu Shin-Yun, Yang Te-Cheng, Liao Tien-Ling, Kao Shu-Huei
Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 106, Taiwan.
Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 106, Taiwan ; School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan.
Oxid Med Cell Longev. 2014;2014:642793. doi: 10.1155/2014/642793. Epub 2014 May 5.
Human peritoneal mesothelial cells (HPMCs) are a critical component of the peritoneal membrane and play a pivotal role in dialysis adequacy. Loss of HPMCs can contribute to complications in peritoneal dialysis. Compelling evidence has shown that high-dialysate glucose is a key factor causing functional changes and cell death in HPMCs. We investigated the mechanism of HPMC apoptosis induced by high-dialysate glucose, particularly the role of mitochondria in the maintenance of HPMCs. HPMCs were incubated at glucose concentrations of 5 mM, 84 mM, 138 mM, and 236 mM. Additionally, N-acetylcysteine (NAC) was used as an antioxidant to clarify the mechanism of high-dialysate-glucose-induced apoptosis. Exposing HPMCs to high-dialysate glucose resulted in substantial apoptosis with cytochrome c release, followed by caspase activation and poly(ADP-ribose) polymerase cleavage. High-dialysate glucose induced excessive reactive oxygen species production and lipid peroxidation as well as oxidative damage to DNA. Mitochondrial fragmentation, multiple mitochondrial DNA deletions, and dissipation of the mitochondrial membrane potential were also observed. The mitochondrial dysfunction and cell death were suppressed using NAC. These results indicated that mitochondrial dysfunction is one of the main causes of high-dialysate-glucose-induced HPMC apoptosis.
人腹膜间皮细胞（HPMCs）是腹膜的关键组成部分，在透析充分性方面发挥着关键作用。HPMCs的丧失会导致腹膜透析并发症。有力证据表明，高透析液葡萄糖是导致HPMCs功能改变和细胞死亡的关键因素。我们研究了高透析液葡萄糖诱导HPMC凋亡的机制，特别是线粒体在维持HPMCs中的作用。将HPMCs在5 mM、84 mM、138 mM和236 mM的葡萄糖浓度下孵育。此外，使用N - 乙酰半胱氨酸（NAC）作为抗氧化剂来阐明高透析液葡萄糖诱导凋亡的机制。将HPMCs暴露于高透析液葡萄糖会导致大量凋亡，伴有细胞色素c释放，随后是半胱天冬酶激活和聚（ADP - 核糖）聚合酶裂解。高透析液葡萄糖诱导过量活性氧生成、脂质过氧化以及DNA氧化损伤。还观察到线粒体碎片化、多个线粒体DNA缺失以及线粒体膜电位耗散。使用NAC可抑制线粒体功能障碍和细胞死亡。这些结果表明，线粒体功能障碍是高透析液葡萄糖诱导HPMC凋亡的主要原因之一。
