Light and glutamate-induced degradation of the circadian oscillating protein BMAL1 during the mammalian clock resetting.
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.
Tamaru
T
T
Department of Physiology, Toho University School of Medicine, Tokyo 143-8540, Japan. tetamaru@med.toho-u.ac.jp.
Isojima
Y
Y
Yamada
T
T
Okada
M
M
Nagai
K
K
Takamatsu
K
K
D056930:ARNTL Transcription Factors; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D051792:Basic Helix-Loop-Helix Proteins; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology*; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D003624:Darkness; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000378:metabolism* / Q000494:pharmacology; D015151:Immunoblotting; D066298:In Vitro Techniques; D008027:Light; D008297:Male; D016202:N-Methylaspartate / Q000378:metabolism / Q000494:pharmacology; D009928:Organ Specificity; D017440:Photoperiod; D051381:Rats; D017208:Rats, Wistar; D013493:Suprachiasmatic Nucleus / Q000187:drug effects / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*
D056930:ARNTL Transcription Factors; D000906:Antibodies; D051792:Basic Helix-Loop-Helix Proteins; D018698:Glutamic Acid; D016202:N-Methylaspartate; D013779:Tetrodotoxin; D014157:Transcription Factors