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CROSS-TALK OF RETINOIC ACID AND ADRENERGIC HORMONE SIGNALING MAY INFLUENCE DEVELOPMENT OF CARDIAC CONDUCTION AND RHYTHMICITY IN UTERO

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Date Issued:
2011
Abstract/Description:
Stress hormones, adrenaline and noradrenaline, have been shown to be critical for heart development. Mice lacking dopamine beta-hydroxylase (Dbh), an enzyme responsible for synthesis of these adrenergic hormones, die during mid-gestation due to cardiac failure. Prior research showed that adrenergic cells are found within the electrical conduction system of the heart, and adrenergic deficiency leads to slowed cardiac conduction during embryogenesis. Microarray analysis of wild-type (Dbh+/+) and knockout (Dbh-/-) mouse hearts revealed significant differences in expression of retinoic acid (RA) signaling genes. RA signaling has also been shown to be critical for heart development. These data suggest that heart failure due to adrenergic deficiency may be dependent upon RA signaling. This led to the hypothesis that adrenergic hormones promote the development of the electrical conduction system through modulation of RA signaling. To test this, embryonic mouse hearts were cultured with LE 135, a RA receptor blocker. Heart rate, arrhythmic index (AI) and conduction time were measured. Under these conditions there was a marked increase in arrhythmias. Hearts treated with LE 135 showed a mean AI of 0.232+/-0.057 after 24 hours of treatment while when untreated had an AI of 0.083+/-0.028 (p<0.05;n=15). In contrast, there was no significant change in heart rate or conduction speed after 24 hours with or without the retinoic acid receptor blocker. To determine if adrenergic stimulus influences retinoic acid response, an established RA-sensitive reporter cell line was employed. These F9-RARE-LacZ cells were treated with forskolin (cAMP regulator) and isoproterenol (beta-agonist) to measure changes in RA signaling. Evaluation of RA signaling showed an increase in retinoic acid responsiveness when treated with an adrenergic signaling agonist. These results suggest that proper retinoic acid signaling is essential for maintaining cardiac rhythmicity during embryonic development and adrenergic stimulation can influence this response.
Title: CROSS-TALK OF RETINOIC ACID AND ADRENERGIC HORMONE SIGNALING MAY INFLUENCE DEVELOPMENT OF CARDIAC CONDUCTION AND RHYTHMICITY IN UTERO.
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Name(s): Alam, Sabikha, Author
Ebert, Steven, Committee Chair
University of Central Florida, Degree Grantor
Type of Resource: text
Date Issued: 2011
Publisher: University of Central Florida
Language(s): English
Abstract/Description: Stress hormones, adrenaline and noradrenaline, have been shown to be critical for heart development. Mice lacking dopamine beta-hydroxylase (Dbh), an enzyme responsible for synthesis of these adrenergic hormones, die during mid-gestation due to cardiac failure. Prior research showed that adrenergic cells are found within the electrical conduction system of the heart, and adrenergic deficiency leads to slowed cardiac conduction during embryogenesis. Microarray analysis of wild-type (Dbh+/+) and knockout (Dbh-/-) mouse hearts revealed significant differences in expression of retinoic acid (RA) signaling genes. RA signaling has also been shown to be critical for heart development. These data suggest that heart failure due to adrenergic deficiency may be dependent upon RA signaling. This led to the hypothesis that adrenergic hormones promote the development of the electrical conduction system through modulation of RA signaling. To test this, embryonic mouse hearts were cultured with LE 135, a RA receptor blocker. Heart rate, arrhythmic index (AI) and conduction time were measured. Under these conditions there was a marked increase in arrhythmias. Hearts treated with LE 135 showed a mean AI of 0.232+/-0.057 after 24 hours of treatment while when untreated had an AI of 0.083+/-0.028 (p<0.05;n=15). In contrast, there was no significant change in heart rate or conduction speed after 24 hours with or without the retinoic acid receptor blocker. To determine if adrenergic stimulus influences retinoic acid response, an established RA-sensitive reporter cell line was employed. These F9-RARE-LacZ cells were treated with forskolin (cAMP regulator) and isoproterenol (beta-agonist) to measure changes in RA signaling. Evaluation of RA signaling showed an increase in retinoic acid responsiveness when treated with an adrenergic signaling agonist. These results suggest that proper retinoic acid signaling is essential for maintaining cardiac rhythmicity during embryonic development and adrenergic stimulation can influence this response.
Identifier: CFH0003831 (IID), ucf:44726 (fedora)
Note(s): 2011-05-01
B.S.
Medicine, Dept. of Molecular Biology and Microbiology
Masters
This record was generated from author submitted information.
Subject(s): Adrenergic hormones
stress hormones
retinoic acid
cardiac rhythm
heart rhythm
cardiac rhythmicity
heart rhythmicity
cardiac conduction
heart conduction
Persistent Link to This Record: http://purl.flvc.org/ucf/fd/CFH0003831
Restrictions on Access: public
Host Institution: UCF

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