Interrelationship between 3,5,3 '-triiodothyronine and the circadian clock in the rodent heart

Interrelationship between 3,5,3 '-triiodothyronine and the circadian clock in the rodent heart

Author Peliciari-Garcia, Rodrigo Antonio Autor UNIFESP Google Scholar
Previde, Rafael Maso Google Scholar
Nunes, Maria Tereza Google Scholar
Young, Martin Elliot Google Scholar
Abstract Triiodothyronine (T3) is an important modulator of cardiac metabolism and function, often through modulation of gene expression. The cardiomyocyte circadian clock is a transcriptionally based molecular mechanismcapable of regulating cardiac processes, in part bymodulating responsiveness of the heart to extra-cardiac stimuli/stresses in a time-of-day (TOD)-dependent manner. Although TOD-dependent oscillations in circulating levels of T3 (and its intermediates) have been established, oscillations in T3 sensitivity in the heart is unknown. To investigate the latter possibility, euthyroid male Wistar rats were treated with vehicle or T3 at distinct times of the day, after which induction of known T3 target genes were assessed in the heart (4-h later). The expression of mRNA was assessed by real-time quantitative polymerase chain reaction (qPCR). Here, we report greater T3 induction of transcript levels at the end of the dark phase. Surprisingly, use of cardiomyocyte-specific clockmutant (CCM) mice revealed that TOD-dependent oscillations in T3 sensitivity were independent of this cell autonomous mechanism. Investigation of genes encoding for proteins that affect T3 sensitivity revealed that Dio1, Dio2 and Thrb1 exhibited TOD-dependent variations in the heart, while Thra1 and Thra2 did not. Of these, Dio1 and Thrb1 were increased in the heart at the end of the dark phase. Interestingly, we observed that T3 acutely altered the expression of core clock components (e.g. Bmal1) in the rat heart. To investigate this further, rats were injected with a single dose of T3, after which expression of clock genes was interrogated at 3-h intervals over the subsequent 24-h period. These studies revealed robust effects of T3 on oscillations of both core clock components and clock-controlled genes. In summary, the current study exposed TOD-dependent sensitivity to T3 in the heart and its effects in the circadian clock genes expression.
Keywords Circadian Clocks
Gene Expression
T3Thyroid-Hormone Action
Dawn Phenomenon
Contractile Function
Rat Cardiomyocytes
Hpt Axis
Language English
Sponsor Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
Conselho Nacional de Pesquisa e Desenvolvimento (CNPq)
Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2013/05629-4]
National Heart, Lung, and Blood Institute [HL106199, HL074259, HL123574, HL122975]
Grant number FAPESP: 2013/05629-4
National Heart, Lung, and Blood Institute: HL106199
National Heart, Lung, and Blood Institute: HL074259
National Heart, Lung, and Blood Institute: HL123574
National Heart, Lung, and Blood Institute: HL122975
Date 2016
Published in Chronobiology International. Philadelphia, v. 33, n. 10, p. 1444-1454, 2016.
ISSN 0742-0528 (Sherpa/Romeo, impact factor)
Publisher Karger
Extent 1444-1454
Access rights Closed access
Type Article
Web of Science ID WOS:000388746800014

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