Light and glutamate-induced degradation of the circadian oscillating protein BMAL1 during the mammalian clock resetting

J Neurosci. 2000 Oct 15;20(20):7525-30. doi: 10.1523/JNEUROSCI.20-20-07525.2000.

Abstract

Recently discovered mammalian clock genes are believed to compose the core oscillator, which generates the circadian rhythm. BMAL1/CLOCK heterodimer is the essential positive element that drives clock-related transcription and self-sustaining oscillation by a negative feedback mechanism. We examined BMAL1 protein expression in the rat suprachiasmatic nuclei (SCN) by immunoblot analysis. Anti-BMAL1 antiserum raised against rBMAL1 recognized 70 kDa mBMAL1b and detected a similar immunoreactivity (IR) as a major band in rat brains. Robust circadian BMAL1-IR oscillations with nocturnal peaks were detected in the SCN during a light/dark cycle and under constant darkness. A short duration light exposure at night acutely reduced BMAL1-IR in the SCN during photoentrainment. This might be attributable to the degradation of BMAL1 protein. Application of glutamate and NMDA to the SCN slices at projected night, a procedure mimicking photic phase delay shift, also acutely reduced BMAL1-IR in a similar manner. A rapid decrease of BMAL1 protein suggests that BMAL1 protein might be implicated in the light-transducing pathway within the SCN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ARNTL Transcription Factors
  • Animals
  • Antibodies / pharmacology
  • Basic Helix-Loop-Helix Transcription Factors
  • Biological Clocks / drug effects
  • Biological Clocks / physiology*
  • Circadian Rhythm / drug effects
  • Circadian Rhythm / physiology*
  • Darkness
  • Dose-Response Relationship, Drug
  • Glutamic Acid / metabolism*
  • Glutamic Acid / pharmacology
  • Immunoblotting
  • In Vitro Techniques
  • Light*
  • Male
  • N-Methylaspartate / metabolism
  • N-Methylaspartate / pharmacology
  • Organ Specificity
  • Photoperiod
  • Rats
  • Rats, Wistar
  • Suprachiasmatic Nucleus / drug effects
  • Suprachiasmatic Nucleus / metabolism
  • Tetrodotoxin / pharmacology
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / metabolism*

Substances

  • ARNTL Transcription Factors
  • Antibodies
  • Basic Helix-Loop-Helix Transcription Factors
  • Transcription Factors
  • Glutamic Acid
  • Tetrodotoxin
  • N-Methylaspartate