Evidence for circadian regulation of activating transcription factor 5 but not tyrosine hydroxylase by the chromaffin cell clock

Dario R. Lemos, Leela Goodspeed, Luciana Tonelli, Marina P. Antoch, Sergio Ojeda, Henryk Urbanski

    Research output: Contribution to journalArticle

    16 Citations (Scopus)

    Abstract

    In mammals, adrenal medulla chromaffin cells constitute a fundamental component of the sympathetic nervous system outflow, producing most of the circulating adrenaline. We recently found that the rhesus monkey adrenal gland expresses several genes in a 24-h rhythmic pattern, including TH (the rate-limiting enzyme in catecholamine synthesis) and Atf5 (a transcription factor involved in apoptosis and neural cell differentiation) together with the core-clock genes. To examine whether these core-clock genes play a role in adrenal circadian function, we exposed rat pheochromocytoma PC12 cells to a serum shock and found that it triggered rhythmic oscillation of the clock genes rBmal1, rPer1, rRev-erbα, and rCry1 and induced the circadian expression of Atf5 but not TH. Furthermore, we found that the CLOCK/brain and muscle Arnt-like protein-1 (BMAL1) heterodimer could regulate Atf5 expression by binding to an E-box motif and repressing activity of its promoter. The physiological relevance of this interaction was evident in Bmal1 -/- mice, in which blunted circadian rhythm of Atf5 mRNA was observed in the liver, together with significantly higher expression levels in both liver and adrenal glands. Although we found no compelling evidence for rhythmic expression of TH in chromaffin cells being regulated by an intrinsic molecular clock mechanism, the Atf5 results raise the possibility that other aspects of chromaffin cell physiology, such as cell survival and cell differentiation, may well be intrinsically regulated.

    Original languageEnglish (US)
    Pages (from-to)5811-5821
    Number of pages11
    JournalEndocrinology
    Volume148
    Issue number12
    DOIs
    StatePublished - Dec 2007

    Fingerprint

    Activating Transcription Factors
    Chromaffin Cells
    Tyrosine 3-Monooxygenase
    Adrenal Glands
    Genes
    Cell Differentiation
    E-Box Elements
    Cell Physiological Phenomena
    Adrenal Medulla
    Liver
    PC12 Cells
    Sympathetic Nervous System
    Pheochromocytoma
    Circadian Rhythm
    Macaca mulatta
    Epinephrine
    Catecholamines
    Mammals
    Shock
    Cell Survival

    ASJC Scopus subject areas

    • Endocrinology
    • Endocrinology, Diabetes and Metabolism

    Cite this

    Evidence for circadian regulation of activating transcription factor 5 but not tyrosine hydroxylase by the chromaffin cell clock. / Lemos, Dario R.; Goodspeed, Leela; Tonelli, Luciana; Antoch, Marina P.; Ojeda, Sergio; Urbanski, Henryk.

    In: Endocrinology, Vol. 148, No. 12, 12.2007, p. 5811-5821.

    Research output: Contribution to journalArticle

    Lemos, Dario R. ; Goodspeed, Leela ; Tonelli, Luciana ; Antoch, Marina P. ; Ojeda, Sergio ; Urbanski, Henryk. / Evidence for circadian regulation of activating transcription factor 5 but not tyrosine hydroxylase by the chromaffin cell clock. In: Endocrinology. 2007 ; Vol. 148, No. 12. pp. 5811-5821.
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