Form Of Angiotensin-converting Enzyme Research Articles

The testicular form of angiotensin converting enzyme as a marker for human sperm quality assessment.

Spermatozoa are rapidly changing cellular structures that are highly dependent on their interaction with the environment. These interactions cause fundamental changes in the spermatozoa's cells and membrane.

SARS-CoV-2 RBD-Specific Antibodies Induced Early in the Pandemic by Natural Infection and Vaccination Display Cross-Variant Binding and Inhibition.

The development of vaccine candidates for COVID-19 has been rapid, and those that are currently approved display high efficacy against the original circulating strains. However, recently, new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged with increased transmission rates and less susceptibility to vaccine induced immunity. A greater understanding of protection mechanisms, including antibody longevity and cross-reactivity towards the variants of concern (VoCs), is needed. In this study, samples collected in Denmark early in the pandemic from paucisymptomatic subjects (n = 165) and symptomatic subjects (n = 57) infected with SARS-CoV-2 were used to assess IgG binding and inhibition in the form of angiotensin-converting enzyme 2 receptor (ACE2) competition against the wild-type and four SARS-CoV-2 VoCs (Alpha, Beta, Gamma, and Omicron). Antibodies induced early in the pandemic via natural infection were cross-reactive and inhibited ACE2 binding of the VoC, with reduced inhibition observed for the Omicron variant. When examined longitudinally, sustained cross-reactive inhibitory responses were found to exist in naturally infected paucisymptomatic subjects. After vaccination, receptor binding domain (RBD)-specific IgG binding increased by at least 3.5-fold and inhibition of ACE2 increased by at least 2-fold. When vaccination regimens were compared (two doses of Pfizer-BioNTech BNT162b2 (n = 50), or one dose of Oxford-AstraZeneca ChAdOx1 nCoV-19 followed by Pfizer-BioNTech BNT162b2 (ChAd/BNT) (n = 15)), higher levels of IgG binding and inhibition were associated with mix and match (ChAd/BNT) prime-boosting and time since vaccination. These results are particularly relevant for countries where vaccination levels are low.

Melatonin, cardiovascular disease and COVID-19: A potential therapeutic strategy?

The mechanism for SARS-CoV-2 infection is the requisite binding of the virus to the membrane-bound form of angiotensin-converting enzyme 2 (ACE2) and internalization of the complex by the host cell. SARS-CoV-2 induced endothelial dysfunction and cardiovascular injury are probably initiated by increases in the phosphorylation levels of JAK2 and STAT3 and resultant reactive oxygen species (ROS) formation. These pathological alterations are speculated to be strikingly reversed by melatonin

Fluorescence polarization studies of different forms of angiotensin-converting enzyme.

The interaction of three forms of bovine angiotensin-converting enzyme (ACE) with the competitive peptide inhibitor lisinopril with a fluorescent label was studied using fluorescence polarization. The dissociation constants Kd of the enzyme-inhibitor complexes in 50 mM Hepes-buffer (pH 7.5) containing 150 mM NaCl and 1 microM ZnCl2 at 37 degrees C were (2.3 +/- 0.4).10(-8), (2.1 +/- 0.3).10(-8), and (2.1 +/- 0.2).10(-8) M for two-domain somatic ACE, single-domain testicular ACE, and for the N-domain of the enzyme, respectively. The interaction of the enzyme with the inhibitor strongly depended on the presence of chloride in the medium, and the apparent dissociation constant of the ACE-chloride complex was (1.3 +/- 0.2).10(-3) M for the somatic enzyme. The dissociation kinetics of the complex of the inhibitor with somatic ACE did not fit the kinetics of a first-order reaction, but it was approximated by a model of simultaneous dissociation of two complexes with the dissociation rate constants (0.13 +/- 0.01) sec(-1) and (0.026 +/- 0.001) sec(-1) that were present at approximately equal initial concentrations. The dissociation kinetics of the single-domain ACE complexes with the inhibitor were apparently first-order, and the dissociation rate constants were similar: (0.055 +/- 0.001) and (0.041 +/- 0.001) sec(-1) for the N-domain and for testicular ACE, respectively.

Limited Proteolysis of Human Kidney Angiotensin-Converting Enzyme and Generation of Catalytically Active N- and C-Terminal Domains

The somatic form of angiotensin converting enzyme is a class I ectoenzyme that is bound to the surface of endothelial calls. It consists of two homologous, catalytic domains of approximately 600 residues each; a juxtamembrane “stalk” region; a transmembrane, hydrophobic sequence; and a 30 residue, C-terminal cytosolic domain. We have used limited proteolysis to probe the structural and functional properties of the enzyme. Endoproteinase Asp-N cleaves both the Thr615- Asp616and the Leu1219- Asp1220peptide bonds to generate the two catalytic domains which were isolated by a combination of immunoaffinity and lisinopril Sepharose affinity chromatography. The enzymatic characteristics of the N and C fragments were examined with angiotensin I, hippuryl-His-Leu, and luteinizing hormone-releasing hormone and indicate that both fragments contain catalytically active sites that retain their individual functional integrity.

A recombinant form of angiotensin converting enzyme expressed from baculovirus-infected insect cells

A secreted form of the C-domain of angiotensin converting enzyme has been expressed from the baculovirus-infected insect cell system. This soluble enzyme was purified by affinity chromatography and characterised in terms of its carbohydrate side chains and binding of substrates and influences.

Immunological studies on the endothelial and testicular forms of angiotensin converting enzyme.

Immunological studies on the endothelial and testicular forms of angiotensin converting enzyme.

Expression of angiotensin converting enzyme mRNA in rat brain

Using molecular genetic approaches, two forms of angiotensin-converting enzyme (ACE) have so far been identified; a pulmonary form and a testicular form. This study utilized both northern blot analysis and in-situ hybridization to examine the expression of ACE mRNA in the rat brain. Northern blot analysis using oligonucleotide probes specific to the testicular or pulmonary forms of ACE demonstrated expression of a 4–5kb mRNA doublet in the rat brain, identical in size to pulmonary ACE mRNA. No expression of the testicular form of ACE mRNA was detected in the brain. In situ hybridization demonstrated that ACE mRNA was expressed in the choroid plexus, caudate putamen and cerebellum. A weak signal was also observed in the hippocampus. This distribution correlated well with the expression of ACE mapped by radioligand binding and autoradiography.

Characterization of neuronal and endothelial forms of angiotensin converting enzyme in pig brain.

The molecular forms of angiotensin converting enzyme (ACE; EC 3.4.15.1) in preparations of pig brain cortical microvessels and striatal synaptosomal membranes have been identified by immunoelectrophoretic blot analysis. The cortical microvessels contained only the endothelial form of the enzyme, Mr 180,000, which comigrated with pig kidney ACE on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In contrast, the synaptosomal membranes contained only a smaller form of ACE, Mr 170,000, which represents the neuronal form of the enzyme. No significant differences in inhibitor sensitivity or substrate specificity were detected between the two forms of ACE. In particular, neurokinin A was resistant to hydrolysis by either microvessel or synaptosomal membrane ACE, and the pattern of hydrolysis of substance P by the two preparations was identical.

Molecular forms of angiotensin-converting enzyme in brain microvessels

Molecular forms of angiotensin-converting enzyme in brain microvessels

Isolation of cDNA clones of rabbit angiotensin converting enzyme: Identification of two distinct mRNAs for the pulmonary and the testicular isozymes

We have isolated cDNA clones of rabbit angiotensin converting enzyme. These clones were isolated by antibody-screening of a lambda gt11 expression library made from rabbit testicular mRNA. The 2.6 kb insert of one such clone was subcloned in pBR322 and used as a hybridization probe. Out of the twenty independently isolated clones only seven hybridized with this probe suggesting that these clones belong to at least two families. Northern analysis revealed the presence of a 2.6 kb mRNA in rabbit testes and a 5.0 kb mRNA in rabbit lungs which hybridized strongly with this probe. These results indicate that the two tissue-specific isozymic forms of angiotensin converting enzyme are encoded by two distinct mRNAs which share sequence homologies.

Substance K and substance P as possible endogenous substrates of angiotensin converting enzyme in the brain

In the brain angiotensin converting enzyme is highly localized to a striatonigral pathway, which contains no endogenous angiotensin. Substance P, also localized to a striatonigral pathway, is degraded by ACE via two different pathways. The lung and striatal isozymes of angiotensin converting enzyme exhibit differential cleavage of substance P, with lung preferring an initial tripeptide cleavage, and striatum an initial dipeptide cleavage. Substance K is degraded by the striatal isozyme but is not cleaved by the lung isozyme. Substance P 5–11 is not cleaved by either form of angiotensin converting enzyme.

Human testicular angiotensin-converting enzyme is a mixture of two molecular weight forms. Only one is similar to the seminal plasma enzyme

Two molecular weight (M r) forms of angiotensin-converting enzyme are present in human testis. Both the high M r 140,000 form and the low M r 90,000 form are catalytically similar but immunologically distinct. After isoelectric focusing, the profile of sialylated M r 140,000 isozymes resembled that of seminal plasma converting enzyme, whereas the nonsialylated M r 90,000 isozymes were distinct. These data suggest that the M r 140,000 testicular converting enzyme may be a source of converting enzyme in seminal plasma.