Abstract
FK506 is an important immunosuppressive medication. However, it can provoke neurotoxicity, nephrotoxicity, and diabetes as adverse side effects. The decrease in oxygen consumption of rat cells treated with pharmacologically relevant concentrations of FK506, along with other evidences, has insinuated that some of the toxic effects are probably caused by drug-induced mitochondrial dysfunction at the level of gene expression. To confirm this suggestion, we have analyzed cell respiration and mitochondrial protein synthesis in human cell lines treated with FK506. This drug provokes an important decrease in oxygen consumption, accompanied by a slight reduction in the synthesis of mitochondria DNA-encoded proteins. These results are similar to those triggered by rapamycin, another macrolide with immunosuppressive properties, therefore insinuating a common toxic pathway.
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Acknowledgments
This work was supported by grants from Instituto de Salud Carlos III [FIS-PI10/00662, PI11/01301, REDINREN-RD06/0016]; Departamento de Ciencia, Tecnología y Universidad del Gobierno de Aragón y Fondo Social Europeo [Grupos Consolidados B33]; and FEDER Funding Program from the European Union. DP-G was supported by the Asociación de Enfermos de Patología Mitocondrial (AEPMI). MP and LL have fellowships from FICYT-Principado de Asturias and Instituto de Salud Carlos III (FI12/00217), respectively. The CIBERER is an initiative of the ISCIII.
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Palacín, M., Coto, E., Llobet, L. et al. FK506 affects mitochondrial protein synthesis and oxygen consumption in human cells. Cell Biol Toxicol 29, 407–414 (2013). https://doi.org/10.1007/s10565-013-9263-0
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DOI: https://doi.org/10.1007/s10565-013-9263-0