Characterization of angiotensin II metabolism by aminopeptidase A.
Item
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Title
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Characterization of angiotensin II metabolism by aminopeptidase A.
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Identifier
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AAI9618106
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identifier
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9618106
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Creator
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Song, Lijun.
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Contributor
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Adviser: Dennis P. Healy
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Date
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1996
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Molecular | Biology, Animal Physiology
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Abstract
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The functions of the renin-angiotensin system (RAS) in regulating blood pressure and fluid volume have been known for a long time. The RAS has been implicated in the development of hypertension. Little is known about the regulation of angiotensin II (AII) metabolism. The first step in the metabolism of AII is by aminopeptidase A (APA) to hydrolyze the N-terminal aspartyl residue of AII to produce AIII, AIII is then degraded into inactive fragments by other peptidases. APA, a membrane-bound ectoenzyme, is generally believed to be an unregulated housekeeping enzyme. In order to understand the functional relationship between AII and APA in AII metabolism, my thesis is focused on the studies of APA localization and APA regulation by AII in rat tissues. In chapter 2, the localization of APA in rat peripheral tissues was studied. APA was localized to capillaries in posterior pituitary, sinusoids of adrenal cortex, and mesangial cells of kidney glomeruli. This localization is consistent with APA influencing blood pressure and fluid volume by affecting AII stimulated secretion of ADH from pituitary, synthesis and release of aldosterone from the adrenal, and renal fluid homeostasis. In chapter 3, the localization of APA in cerebral microvessels was studied, APA was localized to pericytes, suggesting that APA may act as a part of the blood brain barrier and may play an important role in regulating the effects of AII on the brain. In chapter 4, the effect of AII on APA expression in the kidney of chronically AII-infused rats was studied. APA was elevated in glomeruli. In chapter 5, the regulation of APA by AII was studied in two-kidney one clip (2K-1C) Goldblatt hypertensive rats. APA was elevated in glomeruli from both clipped and unclipped kidneys. These results suggest that APA expression is regulated by AII. This is the first example of a bioactive peptide regulating the activity of its degrading peptidase in the peripheral tissues. Furthermore, these results suggest that stimulation of APA activity by AII may be a protective mechanism to minimize the adverse effects of AII in human hypertensive diseases.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
