Taurine reduces FK506-induced generation of ROS and activation of JNK and Bax in Madin Darby canine kidney cells.
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.
Jeon
Seol-Hee
SH
Department of Pharmacology and Toxicology, College of Veterinary Medicine, Chonbuk National University, Jeonju, Republic of Korea.
Park
Hye-Min
HM
Kim
Shang-Jin
SJ
Lee
Mun-Young
MY
Kim
Gi-Beum
GB
Rahman
Md Mizanur
MM
Woo
Jeong-Nam
JN
Kim
In-Shik
IS
Kim
Jin-Shang
JS
Kang
Hyung-Sub
HS
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
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