FK506 affects mitochondrial protein synthesis and oxygen consumption in human cells.
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.
María
M
Palacín
Eliecer
E
Coto
Laura
L
Llobet
David
D
Pacheu-Grau
Julio
J
Montoya
Eduardo
E
Ruiz-Pesini
D000818:Animals; D003920:Diabetes Mellitus / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D008928:Mitochondria / Q000187:drug effects*; D024101:Mitochondrial Proteins / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects*; D051381:Rats; D016559:Tacrolimus / Q000009:adverse effects* / Q000627:therapeutic use
D007166:Immunosuppressive Agents; D024101:Mitochondrial Proteins; D016559:Tacrolimus