Angiotensin II-Induced Protein Kinase D Activation and Regulation of Aldosterone Production

Hdl Handle:
http://hdl.handle.net/10675.2/319879
Title:
Angiotensin II-Induced Protein Kinase D Activation and Regulation of Aldosterone Production
Authors:
Olala, Lawrence O.
Abstract:
Dysregulated aldosterone production leading to hypertension and its associated complications, such as congestive heart failure, cardiac fibrosis and renal failure, are important public health concerns with a huge impact on the economy and patient quality of life. Thus, there is a high level of interest in the development of medical interventions and lifestyle changes to reduce the incidence of hypertension. Stimulation of the adrenal zona glomerulosa with angiotensin II (AngII), potassium (K+) or adrenocorticotropic hormone (ACTH), increases aldosterone production, to result in increased sodium and water retention. We have recently shown a role for the serine/threonine protein kinase D (PKD) in the regulation of acute aldosterone synthesis upon AngII stimulation. In this study, using both molecular and pharmacological approaches, we demonstrate that Src family kinases and protein kinase C (PKC) activate PKD to increase aldosterone production in bovine adrenal glomerulosa cells. We have also shown that PKD positively regulates expression of steroidogenic acute regulatory (StAR) protein, a protein required for cholesterol transport into the mitochondria, and aldosterone synthesis. PKD plays this role, in part, through activating members of the activating transcription factor (ATF)/cAMP response element (CRE-) binding protein (CREB) family of leucine zipper transcription factors. Therefore, we hypothesize that PKC and Src family kinase-mediated PKD activation in response to AngII increases the phosphorylation and activation of ATF-2 and CREB, which bind the StAR proximal promoter thereby resulting in induction of StAR expression and stimulation of steroidogenesis.
Affiliation:
Department of Pathology
Issue Date:
Feb-2013
URI:
http://hdl.handle.net/10675.2/319879
Additional Links:
http://ezproxy.augusta.edu/login?url=http://search.proquest.com/docview/1412317701?accountid=12365
Type:
Dissertation
Language:
en
Appears in Collections:
Theses and Dissertations; Department of Pathology: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorOlala, Lawrence O.en
dc.date.accessioned2014-06-05T22:13:02Z-
dc.date.available2014-06-05T22:13:02Z-
dc.date.issued2013-02-
dc.identifier.urihttp://hdl.handle.net/10675.2/319879-
dc.description.abstractDysregulated aldosterone production leading to hypertension and its associated complications, such as congestive heart failure, cardiac fibrosis and renal failure, are important public health concerns with a huge impact on the economy and patient quality of life. Thus, there is a high level of interest in the development of medical interventions and lifestyle changes to reduce the incidence of hypertension. Stimulation of the adrenal zona glomerulosa with angiotensin II (AngII), potassium (K+) or adrenocorticotropic hormone (ACTH), increases aldosterone production, to result in increased sodium and water retention. We have recently shown a role for the serine/threonine protein kinase D (PKD) in the regulation of acute aldosterone synthesis upon AngII stimulation. In this study, using both molecular and pharmacological approaches, we demonstrate that Src family kinases and protein kinase C (PKC) activate PKD to increase aldosterone production in bovine adrenal glomerulosa cells. We have also shown that PKD positively regulates expression of steroidogenic acute regulatory (StAR) protein, a protein required for cholesterol transport into the mitochondria, and aldosterone synthesis. PKD plays this role, in part, through activating members of the activating transcription factor (ATF)/cAMP response element (CRE-) binding protein (CREB) family of leucine zipper transcription factors. Therefore, we hypothesize that PKC and Src family kinase-mediated PKD activation in response to AngII increases the phosphorylation and activation of ATF-2 and CREB, which bind the StAR proximal promoter thereby resulting in induction of StAR expression and stimulation of steroidogenesis.en
dc.language.isoenen
dc.relation.urlhttp://ezproxy.augusta.edu/login?url=http://search.proquest.com/docview/1412317701?accountid=12365en
dc.rightsCopyright protected. Unauthorized reproduction or use beyond the exceptions granted by the Fair Use clause of U.S. Copyright law may violate federal law.-
dc.subjectAngIIen
dc.subjectPKDen
dc.subjectbovine adrenal glomerulosa cellsen
dc.subjectAldosteroneen
dc.titleAngiotensin II-Induced Protein Kinase D Activation and Regulation of Aldosterone Productionen
dc.typeDissertationen
dc.contributor.departmentDepartment of Pathologyen
dc.description.advisorBollag, Wendy B.en
dc.description.committeeRainey, William; Johnson, John; Fulton, David; Isales, Carlosen
dc.description.degreeDoctor of Philosophy (Ph.D.)-
All Items in Scholarly Commons are protected by copyright, with all rights reserved, unless otherwise indicated.