Establishment of human cell lines showing circadian rhythms of bioluminescence

Neurosci Lett. 2008 Nov 28;446(1):40-4. doi: 10.1016/j.neulet.2008.08.091. Epub 2008 Sep 17.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ARNTL Transcription Factors
  • Antimanic Agents / pharmacology
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Cell Line
  • Circadian Rhythm / physiology*
  • Dexamethasone / pharmacology
  • Dose-Response Relationship, Drug
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism*
  • Gene Expression Regulation / drug effects
  • Glucocorticoids / pharmacology
  • Humans
  • Lithium Chloride / pharmacology
  • Luciferases / genetics
  • Luciferases / metabolism*
  • Luminescent Measurements / methods*
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic / genetics
  • Retinal Pigment Epithelium / cytology
  • Retinal Pigment Epithelium / metabolism

Substances

  • ARNTL Transcription Factors
  • BMAL1 protein, human
  • Antimanic Agents
  • Basic Helix-Loop-Helix Transcription Factors
  • Glucocorticoids
  • Dexamethasone
  • Luciferases
  • Lithium Chloride