Role of SNARE Proteins in Natriuretic Peptide Secretion by the Heart

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Date

2015-01-26

Authors

Natividad, Nikki

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Abstract

The hormones atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are stored and secreted by cardiac myocytes. To date, there is little information reported regarding the cellular mechanisms regulating the release of these hormones. Recent studies have identified soluble N-ethyl-maleimide-sensitive-fusion attachment protein receptors (SNAREs) in the trafficking, docking and fusion of ANP and BNP secretory vesicles. In this study, I characterized the expression profiles of the three SNARE proteins (syntaxin 5A, syntaxin 18, and SNAP29), implicated in constitutive exocytosis, in atrial and ventricular cardiac myocytes. My results suggest that syntaxin 5A, syntaxin 18 and SNAP29 are not important in the constitutive secretion of ANP and may play a role in another protein trafficking pathway. Syntaxin 1A and SNAP25, two SNARE proteins previously characterized in atrial cardiac myocytes, form a complex in adults that has been implicated in the exocytosis of ANP. I investigated the protein expression and promoter activity of these two SNARE proteins in neonatal and adult atrial and ventricular cardiac myocytes. The functional role of syntaxin 1A and SNAP25 was assessed using botulinum neurotoxin C (BoNT/C) and BoNT/A which cleave these SNARE proteins, respectively. Treatment of cardiac myocytes with BoNT/A and BoNT/C suggest that syntaxin 1A and SNAP25 regulate ANP secretion in neonatal cardiac myocytes, albeit low levels. Lastly, I examined the influence of forskolin and phorbol myristate acetate (PMA) on the syntaxin 1A and SNAP25 promoter. The lack of effect of these agents on gene reporter activity suggests that the CRE element in the syntaxin 1A and SNAP25 promoter do not significantly affect transcriptional activity. Overall, my studies demonstrate the developmental changes in SNARE protein expression in the heart, and their potential role in ANP secretion.

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Cellular biology, Physiology, Biology

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