title: Light and glutamate-induced degradation of the circadian oscillating protein BMAL1 during the mammalian clock resetting.
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.
authors.affiliation: Department of Physiology, Toho University School of Medicine, Tokyo 143-8540, Japan. tetamaru@med.toho-u.ac.jp.
authors.forename: T
authors.initials: T
authors.lastname: Tamaru
authors.forename: Y
authors.initials: Y
authors.lastname: Isojima
authors.forename: T
authors.initials: T
authors.lastname: Yamada
authors.forename: M
authors.initials: M
authors.lastname: Okada
authors.forename: K
authors.initials: K
authors.lastname: Nagai
authors.forename: K
authors.initials: K
authors.lastname: Takamatsu
mesh_terms: 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*
chemical_list: D056930:ARNTL Transcription Factors; D000906:Antibodies; D051792:Basic Helix-Loop-Helix Proteins; D018698:Glutamic Acid; D016202:N-Methylaspartate; D013779:Tetrodotoxin; D014157:Transcription Factors