title: Taurine reduces FK506-induced generation of ROS and activation of JNK and Bax in Madin Darby canine kidney cells.
abstract: 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.
authors.affiliation: Department of Pharmacology and Toxicology, College of Veterinary Medicine, Chonbuk National University, Jeonju, Republic of Korea.
authors.forename: Seol-Hee
authors.initials: SH
authors.lastname: Jeon
authors.forename: Hye-Min
authors.initials: HM
authors.lastname: Park
authors.forename: Shang-Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Mun-Young
authors.initials: MY
authors.lastname: Lee
authors.forename: Gi-Beum
authors.initials: GB
authors.lastname: Kim
authors.forename: Md Mizanur
authors.initials: MM
authors.lastname: Rahman
authors.forename: Jeong-Nam
authors.initials: JN
authors.lastname: Woo
authors.forename: In-Shik
authors.initials: IS
authors.lastname: Kim
authors.forename: Jin-Shang
authors.initials: JS
authors.lastname: Kim
authors.forename: Hyung-Sub
authors.initials: HS
authors.lastname: Kang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004285:Dogs; D007166:Immunosuppressive Agents / Q000633:toxicity*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D016559:Tacrolimus / Q000633:toxicity*; D013654:Taurine / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000975:Antioxidants; D007166:Immunosuppressive Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D013654:Taurine; D048031:JNK Mitogen-Activated Protein Kinases; D008274:Magnesium; D002118:Calcium; D016559:Tacrolimus