Angiotensin I Converting Enzyme

Ra, Skidgel; Eg, Erdös

doi:10.1007/978-1-4615-9543-4_4

Cited by 39 publications

(60 citation statements)

References 9 publications

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“…Peptidases are not peptide-specific (38), and ep24.15 and ep24.16 share a series of substrates with ACE (7). Because the physiological function for ACE in the cardiovascular system is well known (20,21), we examined the kinetic parameters of the peptides identified in this study. The ep24.15 and ep24.16 substrates LVVYPWTQRY, VVYPWTQRY, and PVNFKFLSH also interacted with ACE, with K i values ranging from 1.7 M up to 26 M (Table IV).…”

Section: Resultsmentioning

confidence: 99%

Novel Natural Peptide Substrates for Endopeptidase 24.15, Neurolysin, and Angiotensin-converting Enzyme

Rioli

Gozzo²,

Heimann

et al. 2003

Journal of Biological Chemistry

162

165

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The hemoglobin ␣-chain fragment PVNFKFLSH, which we have named hemopressin, produced dose-dependent hypotension in anesthetized rats, starting at 0.001 g/kg. The hypotensive effect of the peptide was potentiated by enalapril only at the lowest peptide dose. These results suggest a role for hemopressin as a vasoactive substance in vivo. The identification of these putative intracellular substrates for ep24.15 and ep24.16 is an important step toward the elucidation of the role of these enzymes within cells. Endopeptidase EC 3.4.24.15 (ep24.15; also referred to as thimet oligopeptidase) and endopeptidase EC 3. 4.24.16 (ep24.16; also referred to as neurolysin) were initially detected in and purified from rat brain homogenates (1, 2). The cloned rat brain ep24.16 (3) showed 80% similarity and 63% identity with the previously cloned rat testis ep24.15 (4). Both peptidases share most of their natural substrates, including bradykinin, neurotensin, opioids, angiotensin I, and gonadotrophinreleasing hormone (5, 6

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Section: Resultsmentioning

confidence: 99%

Novel Natural Peptide Substrates for Endopeptidase 24.15, Neurolysin, and Angiotensin-converting Enzyme

Rioli

Gozzo²,

Heimann

et al. 2003

Journal of Biological Chemistry

162

165

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“…The C-terminal domain of ACE usually anchors it to the plasma membrane in CHO cells (39)(40)(41)(42)(43), but in the fusion protein it was linked directly to the N-domain of B 2 receptors to form a chimeric ACE. Although both enzyme and receptors remained active at the 1:1 ratio of ACE to B 2 , ACE inhibitor neither potentiated BKan nor resensitized the receptors.…”

Section: Discussionmentioning

confidence: 99%

“…ACE inhibitors have multiple entry points to affect the renin-angiotensin (40,41,45) and the kallikrein-kinin systems (6,(13)(14)(15)(30)(31)(32)(33)(46)(47)(48)(49)(50). Besides inhibiting the hydrolysis of ACE substrates, complex formation between ACE and the bradykinin receptors may contribute to the potentiation of B 2 receptor agonists by ACE inhibitors, (15,51) and some endogenous peptides (19).…”

Section: Discussionmentioning

confidence: 99%

Human ACE and bradykinin B ₂ receptors form a complex at the plasma membrane

et al. 2006

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To investigate how angiotensin-I converting enzyme (ACE) inhibitors enhance the actions of bradykinin (BK) on B 2 receptors independent of blocking BK inactivation, we expressed human somatic ACE and B 2 receptors in CHO cells. Bradykinin and its ACE-resistant analogue were the receptor agonists. B 2 fused with green fluorescent protein (GFP) and ACE were coprecipitated with antisera to GFP or ACE shown in Western blots. Immunohistochemistry of fixed cells localized ACE by red color and B 2 -GFP by green. Yellow color on plasma membranes of coexpressing cells also indicated enzyme-receptor complex formation. Using ACE-fused cyan fluorescent protein donor and B 2 -fused yellow fluorescent protein acceptor, we registered fluorescence resonance energy transfer (FRET) by the enhanced fluorescence of donor upon acceptor photo-bleaching, establishing close (within 10 nm) positions of B 2 receptors and ACE. Bradykinin stimulation cointernalized ACE and B 2 receptors. We expressed ACE fused to N-terminus of B 2 receptors, anchoring only receptors to plasma membranes. Here, in contrast to cells where both ACE and B 2 receptors are separately anchored, ACE inhibitors neither enhance activation of chimeric B 2 , nor resensitize desensitized B 2 receptors. Heterodimer formation between ACE and B 2 receptors can be a mechanism for ACE inhibitors to augment kinin activity at cellular level.

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“…5 ACE cleaves the C-terminal dipeptide from Ang I and bradykinin, thus interacting with RAS and the kallikrein-kinin system simultaneously.…”

Section: Angiotensin-converting Enzyme Inhibitorsmentioning

confidence: 99%

Reinventing the ACE inhibitors: some old and new implications of ACE inhibition

2009

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Since their inception, angiotensin-converting enzyme (ACE) inhibitors have been used as first-line therapy for the treatment of cardiovascular and renal diseases. They restore the balance between the vasoconstrictive salt-retentive and hypertrophy-causing peptide angiotensin II (Ang II) and bradykinin, a vasodilatory and natriuretic peptide. As ACE is a promiscuous enzyme, ACE inhibitors alter the metabolism of a number of other vasoactive substances. ACE inhibitors decrease systemic vascular resistance without increasing heart rate and promote natriuresis. They have been proven effective in the treatment of hypertension, and reduce mortality in congestive heart failure and left ventricular dysfunction after myocardial infarction. They inhibit ischemic events and stabilize plaques. Furthermore, they delay the progression of diabetic nephropathy and neuropathy and act as antioxidants. Ongoing studies have elucidated protective roles for them in both memory-related disorders and cancer. INTRODUCTIONIn recent years, stressful and fiercely competitive lifestyles and food habits have compounded the problems of hypertension. Long-standing and stressful, progressively rising hypertension can lead to many disorders, including myocardial infarction (MI), cerebrovascular events, congestive heart failure, peripheral arterial insufficiency, premature mortality 1 and renal dysfunction leading to glomerulosclerosis and kidney artery aneurysm. 2 A number of therapies are available, but angiotensin-converting enzyme (ACE) inhibitors have been the preferred first-line therapy for hypertension, congestive heart failure, left ventricular (LV) systolic dysfunction and MI. 3,4 ACE inhibitors (ACEis) have been in use for the past two decades, and the interest in them is still growing. Recently, the discovery of domain-selective ACEis and new members of the renin-angiotensin system (RAS) (that is, angiotensin-converting enzyme 2) have again fueled the interest of researchers. Some new studies have expanded the already impressive clinical profile of ACEis. This review traces some already known and new facets of ACE inhibition and introduces new advances in the designing of a new generation of ACEis.

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Angiotensin I Converting Enzyme

Cited by 39 publications

References 9 publications

Novel Natural Peptide Substrates for Endopeptidase 24.15, Neurolysin, and Angiotensin-converting Enzyme

Novel Natural Peptide Substrates for Endopeptidase 24.15, Neurolysin, and Angiotensin-converting Enzyme

Human ACE and bradykinin B ₂ receptors form a complex at the plasma membrane

Reinventing the ACE inhibitors: some old and new implications of ACE inhibition

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Angiotensin I Converting Enzyme

Cited by 39 publications

References 9 publications

Novel Natural Peptide Substrates for Endopeptidase 24.15, Neurolysin, and Angiotensin-converting Enzyme

Novel Natural Peptide Substrates for Endopeptidase 24.15, Neurolysin, and Angiotensin-converting Enzyme

Human ACE and bradykinin B 2 receptors form a complex at the plasma membrane

Reinventing the ACE inhibitors: some old and new implications of ACE inhibition

Contact Info

Product

Resources

About

Human ACE and bradykinin B ₂ receptors form a complex at the plasma membrane