The mitochondrion as a primary site of action of glucocorticoids: mitochondrial nucleotide sequences, showing similarity to hormone response elements, confer dexamethasone inducibility to chimaeric genes transfected in LATK- cells.
The hypothesis of a primary action of steroid hormones on mitochondrial gene expression has been supported by the detection of the glucocorticoid receptor in liver mitochondria and the demonstration of the interaction of the receptor with putative mitochondrial HREs. We now show that two putative mitochondrial glucocorticoid response elements present within the cytochrome oxidase subunit I gene (GREI and GREII), linked to a thymidine kinase promoter and to the CAT gene, transfected to LATK- cells, confer dexamethasone inducibility to the CAT gene. As the plasmids were stably transfected, hormone induction was analysed in the nuclear background. This effect is dose dependent and is abolished by the glucocorticoid antagonist RU38486.
Tsiriyotis
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C
Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, Athens, Greece.
Spandidos
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DA
Sekeris
C E
CE
D000818:Animals; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics*; D003907:Dexamethasone / Q000494:pharmacology*; D003576:Electron Transport Complex IV / Q000235:genetics; D005786:Gene Expression Regulation; D017930:Genes, Reporter / Q000235:genetics; D005938:Glucocorticoids / Q000494:pharmacology*; D006727:Hormone Antagonists / Q000494:pharmacology; D015735:Mifepristone / Q000494:pharmacology; D008930:Mitochondria, Liver / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid; D013937:Thymidine Kinase / Q000235:genetics; D014162:Transfection / Q000235:genetics
D004272:DNA, Mitochondrial; D005938:Glucocorticoids; D006727:Hormone Antagonists; D009838:Oligodeoxyribonucleotides; D015735:Mifepristone; D003907:Dexamethasone; D003576:Electron Transport Complex IV; D015500:Chloramphenicol O-Acetyltransferase; D013937:Thymidine Kinase