FK506: an immunosuppressive agent preserving HIF-1 activity.
During transplantation, donor organs or cells are subjected to hypoxia. Hypoxia-inducible factor-1 (HIF-1) is essential for cellular adaptation to hypoxia. Immunosuppressive agents should be used for preventing graft rejection, but of these, rapamycin and cyclosporine A have been reported to inhibit HIF-1. We examined whether or not another important immunosuppressant, FK506, inhibits HIF-1. In contrast to cyclosporine A, FK506 neither inhibits HIF-1alpha expression in 8 different cell lines, nor represses the transcriptional activity of HIF-1. Compared with cyclosporine A, FK506 significantly reduced the apoptotic cell death by hypoxia. FK506 could preserve HIF-1 activity in donor organs subjected to hypoxia.
Kim
Kyung-Eun
KE
Department of Pharmacology, Seoul National University College of Medicine, Seoul, Korea.
Jung
Yu-Jung
YJ
Yeo
Eun-Jin
EJ
Chun
Yang-Sook
YS
Park
Jong-Wan
JW
D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000096:biosynthesis / Q000502:physiology*; D015151:Immunoblotting; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D016559:Tacrolimus / Q000494:pharmacology*; D014158:Transcription, Genetic
D051793:Hypoxia-Inducible Factor 1; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus