Establishment of human cell lines showing circadian rhythms of bioluminescence.
We have established human retinal pigment epithelial cell lines stably expressing the luciferase gene, driven by the human Bmal1 promoter, to obtain human-derived cells that show circadian rhythms of bioluminescence after dexamethasone treatment. The average circadian period of bioluminescence for the obtained clones was 24.07+/-0.48 h. Lithium (10 mM) in the medium significantly lengthened the circadian period of bioluminescence, which is consistent with previous reports, while 2 mM or 5 mM lithium had no effect. This is the first report on the establishment of human-derived cell lines that proliferate infinitely and show circadian rhythms of bioluminescence, and also the first to investigate the effects of low-dose lithium on the circadian rhythms of human-derived cells in vitro. The established cells will be useful for various in vitro studies of human circadian rhythms and for the development of new therapies for human disorders related to circadian rhythm disturbances.
Yoshikawa
Aki
A
Department of Human Genetics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Shimada
Hiroko
H
Numazawa
Kahori
K
Sasaki
Tsukasa
T
Ikeda
Masaaki
M
Kawashima
Minae
M
Kato
Nobumasa
N
Tokunaga
Katsushi
K
Ebisawa
Takashi
T
D056930:ARNTL Transcription Factors; D018692:Antimanic Agents / Q000494:pharmacology; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D002460:Cell Line; D002940:Circadian Rhythm / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D018021:Lithium Chloride / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism*; D008163:Luminescent Measurements / Q000379:methods*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000378:metabolism
D056930:ARNTL Transcription Factors; D018692:Antimanic Agents; D051792:Basic Helix-Loop-Helix Proteins; D003907:Dexamethasone; D005938:Glucocorticoids; D018021:Lithium Chloride; D008156:Luciferases; C538960:BMAL1 protein, human