Characterization of three aminopeptidases purified from maternal serum

Lalu, Kaisa; Lampelo, Saara; Vanha‐Perttula, T.

doi:10.1016/0167-4838(86)90045-2

Cited by 47 publications

(30 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…to Glu and Asp) measured in the presence of Ca 2ϩ are also comparable with other preparations reported so far (13), further suggesting that the N-terminal cytosolic and transmembrane domains of the enzyme are not essential for the enzymatic activity, and soluble enzyme retains the characteristic enzymatic features of the membrane-bound enzyme (32,34). Moreover, as discussed below, hydrolytic activity of sAPA toward Glu-and Asp-MCA is up-regulated comparably to native enzymes reported to date (11,13,17,35,36).…”

Section: Discussionsupporting

confidence: 67%

“…It was reported that the C-terminal domain but not the interchain disulfide is required for the correct folding and function of APA (22,23). In addition, besides the membrane-bound form, several groups purified APA from retro-placental serum (32,33), indicating that native APA also exists as a soluble form. Available data indicate that K m values of sAPA toward Glu-NA and Asp-NA measured in the presence of Ca 2ϩ are comparable with those of the membrane-bound form of APA (18).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Enzymatic Properties of Human Aminopeptidase A

Goto

Hattori

Ishii

et al. 2006

Journal of Biological Chemistry

View full text Add to dashboard Cite

Aminopeptidase A (APA) is a type II membrane-bound protein implicated in the regulation of blood pressure in the brain renin-angiotensin system. In this study, a recombinant soluble form of APA was expressed in a baculovirus system, purified to homogeneity, and characterized. By using synthetic substrates, it was shown that although the enzyme has a rather broad substrate specificity in the absence of Ca 2؉ , the preferential release of acidic amino acid residues was observed in the presence of Ca 2؉ . Moreover, Ca 2؉ up-or down-regulated the enzymatic activity depending on the substrate. By searching for natural substrates of APA, we found that peptides having acidic amino acids at their N terminus (angiotensin II, neurokinin B, cholecystokinin-8, and chromogranin A) were cleaved by the enzyme efficiently in the presence but not in the absence of Ca 2؉ . Moreover kallidin (Lys-bradykinin) was converted to bradykinin effectively only in the absence of Ca 2؉ . These results suggest that Ca 2؉ increases the preference of the enzyme for the peptide substrates having N-terminal acidic amino acids. In addition, we found that angiotensin IV could bind to APA both in the presence and absence of Ca 2؉ and inhibited the enzymatic activity of APA competitively, suggesting that angiotensin IV acts as a negative regulator of the enzyme once generated from angiotensin II by the serial actions of aminopeptidases. Taken together, these results suggest that there exists a complex regulation of the enzymatic activity of APA, which may contribute to homeostasis such as regulation of blood pressure, maintenance of memory, and normal pregnancy by controlling the concentrations of peptide substrates.

show abstract

Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Enzymatic Properties of Human Aminopeptidase A

Goto

Hattori

Ishii

et al. 2006

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Some other metal ions, coinplexing agents and amino acids are inhibitors (13,33,37,43,47). A very potent inhibitor is amastatin and, to a lesser degree, bestatin and puromycin (15,37). The pH optimum of alanine aminopeptidase is buffer-and substrate-dependent, generally between pH 6.5-8.5 (48)(49)(50).…”

Section: Alanine Aminopeptidasementioning

confidence: 99%

Human Aminopeptidases: A Review of the Literature

Sanderink¹,

Artur²,

Siest³

1988

Clinical Chemistry and Laboratory Medicine

View full text Add to dashboard Cite

Summary:The aminopeptidases constitute a group of enzymes with closely related activities. In clinical chemistry the analysis of the aminopeptidases and of their multiple forms in serum has for a long time been hindered by considerable confusion concerning their identification, and by a lack of characterization. This is in part due to the often large, and sometimes overlapping substrate specificities of the aminopeptidases. This paper reviews the biochemical properties of the different aminopeptidases, the specificities of the assays used for their analysis in serum, some aspects of their multiple forms -which are especially known to occur for alanine äminopeptidase (EC 3.4.11.2) -and the importance of the determination of aminopeptidases and their multiple forms in clinical chemistry.

show abstract

“…APN is widely distributed in many cell types, and its role in hydrolyzing unsubstituted N-terminal residues with neutral side chains varies in different locations. In the epithelium of the renal proximal tubule, APN cleaves its only known natural substrate, angiotensin (ang) III, to ang IV; in synaptic membranes, APN metabolizes enkephalins and endorphins; in the heart, it is an integral component of cardiac remodeling postmyocardial infarction (5)(6)(7)(8)(9)(10); and in the respiratory system, APN is the cell surface receptor for certain human coronaviruses and potentially for the severe acute respiratory syndrome (SARS) virus (11)(12)(13). Additionally, APN functions in signal transduction, cell cycle control, and differentiation (14,15).…”

mentioning

confidence: 99%

Impaired angiogenesis in aminopeptidase N-null mice

Rangel

Sun

Guzman-Rojas

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

114

View full text Add to dashboard Cite

Aminopeptidase N (APN, CD13; EC 3.4.11.2) is a transmembrane metalloprotease with several functions, depending on the cell type and tissue environment. In tumor vasculature, APN is overexpressed in the endothelium and promotes angiogenesis. However, there have been no reports of in vivo inactivation of the APN gene to validate these findings. Here we evaluated, by targeted disruption of the APN gene, whether APN participates in blood vessel formation and function under normal conditions. Surprisingly, APN-null mice developed with no gross or histological abnormalities. Standard neurological, cardiovascular, metabolic, locomotor, and hematological studies revealed no alterations. Nonetheless, in oxygen-induced retinopathy experiments, APN-deficient mice had a marked and dose-dependent deficiency of the expected retinal neovascularization. Moreover, gelfoams embedded with growth factors failed to induce functional blood vessel formation in APNnull mice. These findings establish that APN-null mice develop normally without physiological alterations and can undergo physiological angiogenesis but show a severely impaired angiogenic response under pathological conditions. Finally, in addition to vascular biology research, APN-null mice may be useful reagents in other medical fields such as malignant, cardiovascular, immunological, or infectious diseases.CD13 ͉ knockout mice ͉ retinopathy ͉ vasculogenesis T he aminopeptidases are a large family of proteolytic enzymes that affect protein maturation, degradation, and regulation (1, 2). Aminopeptidase N (APN) is a membrane-bound zincdependent metalloprotease originally identified as a surface marker in myeloid cells (3,4). APN is widely distributed in many cell types, and its role in hydrolyzing unsubstituted N-terminal residues with neutral side chains varies in different locations. In the epithelium of the renal proximal tubule, APN cleaves its only known natural substrate, angiotensin (ang) III, to ang IV; in synaptic membranes, APN metabolizes enkephalins and endorphins; in the heart, it is an integral component of cardiac remodeling postmyocardial infarction (5-10); and in the respiratory system, APN is the cell surface receptor for certain human coronaviruses and potentially for the severe acute respiratory syndrome (SARS) virus (11-13). Additionally, APN functions in signal transduction, cell cycle control, and differentiation (14, 15).We have developed an in vivo system by using ligand peptides displayed on the surface of phage to study organ-and tumorspecific vascular homing; this methodology enables the identification of vascular markers (16,17). We have isolated phage displaying an asparagine-glycine-arginine (NGR)-containing peptide in a tumor-homing selection and have shown that these phage bind selectively to angiogenic blood vessels. When coupled to a cytotoxic drug (18) or fused to a proapoptotic peptide (19) or to tumor necrosis factor (20), NGR-targeted compounds were more effective and less toxic than the respective controls. The cell surface receptor fo...

show abstract

Characterization of three aminopeptidases purified from maternal serum

Cited by 47 publications

References 14 publications

Enzymatic Properties of Human Aminopeptidase A

Enzymatic Properties of Human Aminopeptidase A

Human Aminopeptidases: A Review of the Literature

Impaired angiogenesis in aminopeptidase N-null mice

Contact Info

Product

Resources

About