Department of Pharmacology and Toxicology, College of Veterinary Medicine, Chonbuk National University, Jeonju, Republic of Korea.
Hum Exp Toxicol. 2010 Aug;29(8):627-33. doi: 10.1177/0960327109359019. Epub 2010 Jan 7.
The immunosuppressive compound FK506 has been successfully used in kidney and liver transplant recipients. However, the compound can induce significant side effects on kidney function. Taurine is a potent free radical scavenger that attenuates a variety of renal diseases that are the consequence of excessive oxygen free radical damage. The purpose of this study was to investigate FK506-mediated death of Madin Darby canine kidney (MDCK) cells, in relation to reactive oxygen species (ROS) production. We determined the calcium (Ca(2+)) and magnesium (Mg(2+)) concentration in cultured MDCK cells by microfluorescence techniques and the level of activation of c-Jun-N-terminal kinase (JNK), extracellular signal regulated kinases (ERK), Bcl-2 and Bax proteins by Western blot. Treatment with 10 muM FK506 induced apoptosis in MDCK cells by increasing the level of intracellular ROS and Ca(2+) and by decreaseing the level of intracellular Mg(2+). This increase in intracellular ROS promoted JNK and Bax activation, which increased FK506-induced MDCK cell death. Taurine reduced the FK506-induced generation of ROS and activation of JNK and Bax. The results indicate that taurine can prevent FK506-induced kidney toxicity.
免疫抑制剂 FK506 已成功用于肾和肝移植受者。然而，该化合物会对肾功能产生显著的副作用。牛磺酸是一种有效的自由基清除剂，可减轻多种由氧自由基过度损伤引起的肾脏疾病。本研究旨在探讨 FK506 介导的 Madin Darby 犬肾 (MDCK) 细胞死亡与活性氧 (ROS) 产生的关系。我们通过微荧光技术测定培养的 MDCK 细胞中的钙 (Ca(2+)) 和镁 (Mg(2+)) 浓度，并通过 Western blot 测定 c-Jun-N-末端激酶 (JNK)、细胞外信号调节激酶 (ERK)、Bcl-2 和 Bax 蛋白的激活水平。用 10 μM FK506 处理会通过增加细胞内 ROS 和 Ca(2+) 的水平以及降低细胞内 Mg(2+) 的水平诱导 MDCK 细胞凋亡。这种细胞内 ROS 的增加促进了 JNK 和 Bax 的激活，从而增加了 FK506 诱导的 MDCK 细胞死亡。牛磺酸可减少 FK506 诱导的 ROS 产生和 JNK 和 Bax 的激活。结果表明，牛磺酸可预防 FK506 诱导的肾毒性。
