Evidence for the presence of dipeptidyl carboxypeptidase and its inhibitors in inflammatory synovial fluids

Elisseeva, Yu. E.; Pavlikhina, L. V.; Orekhovich, V. N.; Giacomello, Alessandro; Salerno, C; Fasella, P.

doi:10.1016/0005-2744(81)90260-6

Cited by 2 publications

(2 citation statements)

References 9 publications

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“…Binevski (Moscow State University, Russia). Enzymatic activities of ACE domains were regularly measured by a fluorometric method using the Z‐Phe‐His‐Leu substrate as described previously 25. Briefly, the 2 mL reaction mixture contained barbital buffer (25 mM, pH 7.4), NaCl (50 mM for N‐ACE assay or 200 mM for C‐ACE assay), ZnCl 2 (1 µM), N‐ACE (0.02 µM) or C‐ACE (0.02 µM), Z‐Phe‐His‐Leu (50 µM), which was added last to initiate the reaction.…”

Section: Methodsmentioning

confidence: 99%

The N‐domain of angiotensin‐converting enzyme specifically hydrolyzes the Arg‐5‐His‐6 bond of Alzheimer's Aβ‐(1‐16) peptide and its isoAsp‐7 analogue with different efficiency as evidenced by quantitative matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry

Toropygin

Kugaevskaya

Mirgorodskaya

et al. 2007

Rapid Comm Mass Spectrometry

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Chronic imbalance between production and degradation of the human amyloid-beta peptide (Abeta) is assumed to play an important role in pathogenesis of Alzheimer's disease (AD). Post-translational modifications of Abeta could influence its interactions with specifically cleaving proteases and, therefore, perturb the Abeta homeostasis. The angiotensin-converting enzyme (ACE) was previously shown to degrade non-modified Abeta in vitro and in cells. In the presented work, we investigated the effect of isomerization of Asp-7, a common non-enzymatic age-related modification found in AD-associated Abeta species, on hydrolysis of Abeta by ACE. Two synthetic peptides corresponding to the Abeta region 1-16 with either Asp or isoAsp residues in position 7 were examined as monomeric soluble substrates for the N- as well as for the C-domain of ACE. The use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) coupled with the (18)O-labeled internal standard approach has allowed us to show that (i) the N-domain of ACE (N-ACE), but not the C-domain, selectively cleaves the Arg-5-His-6 bond in both peptides, and that (ii) N-ACE hydrolyzes the isoAsp-7 analogue more efficiently than the non-modified one. Our results demonstrate a new endopeptidase activity of N-ACE as well as high preference of the domain to recognize and hydrolyze the isomerized Abeta species that were earlier suggested to promote AD pathogenesis. The results suggest the need for further analysis of biological effects of isomerized Abeta and its interaction with ACE in AD pathogenesis.

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Section: Methodsmentioning

confidence: 99%

The N‐domain of angiotensin‐converting enzyme specifically hydrolyzes the Arg‐5‐His‐6 bond of Alzheimer's Aβ‐(1‐16) peptide and its isoAsp‐7 analogue with different efficiency as evidenced by quantitative matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry

Toropygin

Kugaevskaya

Mirgorodskaya

et al. 2007

Rapid Comm Mass Spectrometry

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“…В настоящее время нами проводится исследование уровня активности АПФ [68] при плоскоклеточной карциноме шейки матки в опухолевых тканях и в прилегающей к опухоли морфологически нормальной ткани, а также в тканевых лентах, расположенных на протяжении от стенки влагалища до дна полости матки, отобранных на базе отдела патологической анатомии. Активность АПФ в большинстве была существенно выше в опухолях, чем в ткани, прилегающей к опухоли (на 30%-300%) (рис.…”

Section: изучение роли апф при плоскоклеточной карциноме шейки маткиunclassified

Angiotensin converting enzyme: the antigenic properties of the domain, role in alzheimer's disease and tumor progression

Timoshenko

2015

BIOMED KHIM

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Angiotensin converting enzyme (ACE, EC 3.4.15.1) was discovered and characterized in the Laboratory of biochemistry and chemical pathology of proteins under the direction of academician V.N. Orekhovich, where its physiological function, associated with a key role in the regulation of the renin-angiotensin (RAS) and the kallikrein-kinin systems that control blood flow in the body and homeostasis was first deciphered. We carried out a search for structural differences between the two highly homologous domains (N- and C-domains) of somatic ACE (sACE); it was based on a comparative analysis of antigenic determinants (or B-epitopes) of both domains. The revealed epitopes were classified with variable and conserved regions and functionally important sites of the molecule ACE. Essential difference was demonstrated between locations of the epitopes in the N- and C-domains. These data indicate the existence of structural differences between the domains of sACE. We studied the role of the domains of ACE in the metabolism of human amyloid beta peptide (Ab) – the main component of senile plaques, found in the brains of patients with Alzheimer's disease (AD). Our results demonstrated that only N-domain ACE cleaved the Ab between residues R5–H6, while, the C-domain of ACE failed to hydrolyze this region. In addition, the effect of post-translational modifications of Ab on its hydrolysis by the ACE was investigated. We show that isomerization of residue D7, a common non-enzymatic age-related modification found in AD-associated species, does not reduce the affinity of the peptide to the N-domain of ACE, and conversely, it increases. According to our data, the role of ACE in the metabolism of Ab becomes more significant in the development of AD. RAS is involved in malignant transformation and tumor progression. RAS components, including ACE and angiotensin II receptors type 1 (AT1R) are expressed in various human tumors. We found a significant increase in the level of ACE activity in the tumor tissue of squamous cell carcinoma of the cervix. In our viewpoint, the increase in ACE activity may be a marker of poor clinical prognosis.

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Evidence for the presence of dipeptidyl carboxypeptidase and its inhibitors in inflammatory synovial fluids

Cited by 2 publications

References 9 publications

Angiotensin converting enzyme: the antigenic properties of the domain, role in alzheimer's disease and tumor progression

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