Role of SNARE Proteins in Natriuretic Peptide Secretion by the Heart

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dc.contributor.advisorTsushima, Robert
dc.creatorNatividad, Nikki
dc.date.accessioned2015-01-26T15:03:54Z
dc.date.available2015-01-26T15:03:54Z
dc.date.copyright2014-08-20
dc.date.issued2015-01-26
dc.date.updated2015-01-26T15:03:54Z
dc.degree.disciplineBiology
dc.degree.levelMaster's
dc.degree.nameMSc - Master of Science
dc.description.abstractThe 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.
dc.identifier.urihttp://hdl.handle.net/10315/28260
dc.language.isoen
dc.rightsAuthor owns copyright, except where explicitly noted. Please contact the author directly with licensing requests.
dc.subjectCellular biology
dc.subjectPhysiology
dc.subjectBiology
dc.subject.keywordsCardiac myocyteen_US
dc.subject.keywordsAtrial natriuretic peptideen_US
dc.subject.keywordsSNARE proteinsen_US
dc.subject.keywordsHeart diseaseen_US
dc.subject.keywordsSyntaxin 5Aen_US
dc.subject.keywordsSyntaxin 18en_US
dc.subject.keywordsSNAP29en_US
dc.subject.keywordsSyntaxin 1Aen_US
dc.subject.keywordsSNAP25en_US
dc.subject.keywordsCardiac physiologyen_US
dc.subject.keywordsConstitutive exocytosisen_US
dc.titleRole of SNARE Proteins in Natriuretic Peptide Secretion by the Heart
dc.typeElectronic Thesis or Dissertationen_US

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