The Preparation and Function of the Hypertensin-Converting Enzyme

Skeggs, Leonard T.; Kahn, Joseph R.; Shumway, Norman P.

doi:10.1084/jem.103.3.295

Cited by 929 publications

(368 citation statements)

References 5 publications

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“…Skeggs's group was the first to successfully purify Ang I and Ang II from horse plasma with large quantities of hog renin [3][4][5]. Subsequent studies by this same group characterized ACE, the enzyme which converts Ang I to Ang II [6]. Fig 1 shows the biochemical pathways of formation of active angiotensins from their prohormone, angiotensinogen.…”

Section: Introductionmentioning

confidence: 99%

The angiotensin II type 1 receptor and receptor-associated proteins

et al. 2001

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The mechanisms of regulation, activation and signal transduction of the angiotensin II (Ang II) type 1 (AT1) receptor have been studied extensively in the decade after its cloning. The AT1 receptor is a major component of the renin-angiotensin system (RAS). It mediates the classical biological actions of Ang II. Among the structures required for regulation and activation of the receptor, its carboxyl-terminal region plays crucial roles in receptor internalization, desensitization and phosphorylation. The mechanisms involved in heterotrimeric G-protein coupling to the receptor, activation of the downstream signaling pathway by G proteins and the Ang II signal transduction pathways leading to specific cellular responses are discussed. In addition, recent work on the identification and characterization of novel proteins associated with carboxyl-terminus of the AT1 receptor is presented. These novel proteins will advance our understanding of how the receptor is internalized and recycled as they provide molecular mechanisms for the activation and regulation of G-protein-coupled receptors.

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Section: Introductionmentioning

confidence: 99%

The angiotensin II type 1 receptor and receptor-associated proteins

et al. 2001

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“…Renin is released into the bloodstream and cleaves angiotensinogen to produce Ang I, which is subsequently cleaved by angiotensin converting enzyme (ACE) to generate Ang II [35]. Ang II has two main receptors, the angiotensin type 1 and type 2 receptors (AT 1 R and AT 2 R, respectively).…”

Section: Experimental Models Of Hypertensionmentioning

confidence: 99%

Utilizing proteomics to understand and define hypertension: where are we and where do we go?

Delles

Carrick

Graham

et al. 2018

Expert Review of Proteomics

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Introduction: Hypertension is a complex and multifactorial cardiovascular disorder. With different mechanisms contributing to a different extent to an individual’s blood pressure, the discovery of novel pathogenetic principles of hypertension is challenging. However, there is an urgent and unmet clinical need to improve prevention, detection, and therapy of hypertension in order to reduce the global burden associated with hypertension-related cardiovascular diseases.Areas covered: Proteomic techniques have been applied in reductionist experimental models including angiotensin II infusion models in rodents and the spontaneously hypertensive rat in order to unravel mechanisms involved in blood pressure control and end organ damage. In humans proteomic studies mainly focus on prediction and detection of organ damage, particularly of heart failure and renal disease. While there are only few proteomic studies specifically addressing human primary hypertension, there are more data available in hypertensive disorders in pregnancy, such as preeclampsia. We will review these studies and discuss implications of proteomics on precision medicine approaches.Expert commentary: Despite the potential of proteomic studies in hypertension there has been moderate progress in this area of research. Standardized large-scale studies are required in order to make best use of the potential that proteomics offers in hypertension and other cardiovascular diseases.

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“…The enzyme plays an important role in blood pressure regulation by converting the inactive decapeptide angiotensin I to the potent vasopressor angiotensin II (Skeggs et al 1956) and inactivating the vasodilator bradykinin (Yang et al 1970). The enzyme is also able to hydrolyze other naturally occurring peptides, such as N-Acetyl-Seryl-Aspartyl-Lysyl-Proline (Rousseau et al 1995), substance P (Skidgel et al 1984) and luteinizing hormone-releasing hormone ( Skidgel and Erdos 1985).…”

Section: Introductionmentioning

confidence: 99%

The use of Fluorescence Resonance Energy Transfer (FRET) peptidesfor measurement of clinically important proteolytic enzymes

Carmona

Juliano

2009

An. Acad. Bras. Ciênc.

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Proteolytic enzymes have a fundamental role in many biological processes and are associated with multiple pathological conditions. Therefore, targeting these enzymes may be important for a better understanding of their function and development of therapeutic inhibitors. Fluorescence Resonance Energy Transfer (FRET) peptides are convenient tools for the study of peptidases specificity as they allow monitoring of the reaction on a continuous basis, providing a rapid method for the determination of enzymatic activity. Hydrolysis of a peptide bond between the donor/acceptor pair generates fluorescence that permits the measurement of the activity of nanomolar concentrations of the enzyme. The assays can be performed directly in a cuvette of the fluorimeter or adapted for determinations in a 96-well fluorescence plate reader. The synthesis of FRET peptides containing ortho-aminobenzoic acid (Abz) as fluorescent group and 2,4-dinitrophenyl (Dnp) or N-(2,4-dinitrophenyl)ethylenediamine (EDDnp) as quencher was optimized by our group and became an important line of research at the Department of Biophysics of the Federal University of São Paulo. Recently, Abz/Dnp FRET peptide libraries were developed allowing high-throughput screening of peptidases substrate specificity. This review presents the consolidation of our research activities undertaken between 1993 and 2008 on the synthesis of peptides and study of peptidases specificities.

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The Preparation and Function of the Hypertensin-Converting Enzyme

Cited by 929 publications

References 5 publications

The angiotensin II type 1 receptor and receptor-associated proteins

The angiotensin II type 1 receptor and receptor-associated proteins

Utilizing proteomics to understand and define hypertension: where are we and where do we go?

The use of Fluorescence Resonance Energy Transfer (FRET) peptidesfor measurement of clinically important proteolytic enzymes

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