scholarly journals A Novel Protease Inhibitor of the α2-Macroglobulin Family Expressed in the Human Epidermis

2005 ◽  
Vol 281 (9) ◽  
pp. 5780-5789 ◽  
Author(s):  
Marie-Florence Galliano ◽  
Eve Toulza ◽  
Hélène Gallinaro ◽  
Nathalie Jonca ◽  
Akemi Ishida-Yamamoto ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
Human Epidermis ◽  
Α2 Macroglobulin

scholarly journals α2-Macroglobulin-like protein 1 can conjugate and inhibit proteases through their hydroxyl groups, because of an enhanced reactivity of its thiol ester

2020 ◽  
Vol 295 (49) ◽  
pp. 16732-16742 ◽  
Author(s):  
Seandean Lykke Harwood ◽  
Nadia Sukusu Nielsen ◽  
Kathrine Tejlgård Jensen ◽  
Peter Kresten Nielsen ◽  
Ida B. Thøgersen ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
Primary Amines ◽  
Hydroxyl Groups ◽  
Histidine Residue ◽  
Protease Inhibition ◽  
Complement Components ◽  
Proteolytic Activation ◽  
Thiol Ester ◽  
Thiol Esters ◽  
Α2 Macroglobulin

Proteins in the α-macroglobulin (αM) superfamily use thiol esters to form covalent conjugation products upon their proteolytic activation. αM protease inhibitors use theirs to conjugate proteases and preferentially react with primary amines (e.g. on lysine side chains), whereas those of αM complement components C3 and C4B have an increased hydroxyl reactivity that is conveyed by a conserved histidine residue and allows conjugation to cell surface glycans. Human α2-macroglobulin–like protein 1 (A2ML1) is a monomeric protease inhibitor but has the hydroxyl reactivity–conveying histidine residue. Here, we have investigated the role of hydroxyl reactivity in a protease inhibitor by comparing recombinant WT A2ML1 and the A2ML1 H1084N mutant in which this histidine is removed. Both of A2ML1s' thiol esters were reactive toward the amine substrate glycine, but only WT A2ML1 reacted with the hydroxyl substrate glycerol, demonstrating that His-1084 increases the hydroxyl reactivity of A2ML1's thiol ester. Although both A2ML1s conjugated and inhibited thermolysin, His-1084 was required for the conjugation and inhibition of acetylated thermolysin, which lacks primary amines. Using MS, we identified an ester bond formed between a thermolysin serine residue and the A2ML1 thiol ester. These results demonstrate that a histidine-enhanced hydroxyl reactivity can contribute to protease inhibition by an αM protein. His-1084 did not improve A2ML1's protease inhibition at pH 5, indicating that A2ML1's hydroxyl reactivity is not an adaption to its acidic epidermal environment.

Natural anti-proteases in rainbow trout, Oncorhynchus mykiss and brook charr, Salvelinus fontinalis and the in vitro neutralization of fish α2-macroglobulin by the metalloprotease from the pathogenic haemoflagellate, Cryptobia salmositica

Parasitology ◽  
1997 ◽  
Vol 114 (4) ◽  
pp. 375-382 ◽  
Author(s):  
X. ZUO ◽  
P. T. K. WOO
Keyword(s):  
Rainbow Trout ◽  
Protease Inhibitor ◽  
Oncorhynchus Mykiss ◽  
Proteolytic Activity ◽  
Blood Cells ◽  
Salvelinus Fontinalis ◽  
Brook Charr ◽  
Rainbow Trout Oncorhynchus Mykiss ◽  
Α2 Macroglobulin

Natural anti-proteases (α1-protease inhibitor (α1-PI; α1-antitrypsin) and α2-macroglobulin (α2-M)) were found in the blood of rainbow trout, Oncorhynchus mykiss and brook charr, Salvelinus fontinalis. The α2-M inhibited Cryptobia salmositica proteases and was significantly higher in brook charr than in rainbow trout. Under in vitro conditions it took longer for the same number of parasites to neutralize the α2-M in charr than in trout blood. The haemolysis which occurred when C. salmositica was incubated in the blood of rainbow trout was due to neutralization of α2-M. This in vitro study also showed that it was the metalloprotease of C. salmositica that lysed red blood cells and the plasma of the two species of fishes initially prevented haemolysis by inhibiting the proteolytic activity. We suggest that the natural plasma α2-M plays an important role in defence against cryptobiosis in fishes.

scholarly journals A derivative of the plasma protease inhibitor α2-macroglobulin regulates the response to peripheral nerve injury

2007 ◽  
Vol 103 (2) ◽  
pp. 694-705 ◽  
Author(s):  
Sanja Arandjelovic ◽  
Nikola Dragojlovic ◽  
Xiaoqing Li ◽  
Robert R. Myers ◽  
W. Marie Campana ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Protease Inhibitor ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Α2 Macroglobulin

scholarly journals Activity of kallikrein-kinin system in children in norm and at some pathological states

2009 ◽  
Vol 8 (4(2)) ◽  
pp. 61-69
Author(s):  
Ye. I. Kondratiyeva ◽  
T. Ye. Tropova ◽  
G. A. Sukhanova ◽  
A. A. Terentiyeva ◽  
T. S. Krivonogova ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Protease Inhibitor ◽  
Blood Plasma ◽  
Inflammatory Diseases ◽  
Healthy Children ◽  
Urinary System ◽  
Kinin System ◽  
Α2 Macroglobulin ◽  
Kallikrein Kinin System ◽  
Ischemic Encephalopathy

Proteolytic systems of tissue and blood plasma take part in the processes of adaptation and protection of an organism, as well as in development of pathological reactions. We have studied the activity of kallikrein, kallikreinogen, angiotensine transforming enzyme, α1-protease inhibitor, and α2-macroglobulin in healthy children in different age periods, in newborns with hypoxic-ischemic encephalopathy, in children with infectious-inflammatory diseases of the urinary system, obesity, and metabolic syndrome.The activity of the kallikrein-kinin system was increased in all the groups against the background of the decreased inhibitory activity of blood plasma of different intensity, which can be used for the prediction of the course of diseases.

Tissue and plasma elastase and anti-protease (α1 protease inhibitor-α2 macroglobulin) levels in malignancies of head and neck

1993 ◽  
Vol 21 (3) ◽  
pp. 307S-307S ◽  
Author(s):  
GÜLDAL KIRKALI ◽  
YASEMIN BASKIN ◽  
GÜL GÜNER ◽  
TARIK ŞSLENGÖR ◽  
KERIM CERYAN
Keyword(s):  
Protease Inhibitor ◽  
Head And Neck ◽  
Α2 Macroglobulin

scholarly journals Unique Features of a Pseudomonas aeruginosa α2-Macroglobulin Homolog

mBio ◽  
2013 ◽  
Vol 4 (4) ◽  
Author(s):  
Mylène Robert-Genthon ◽  
Maria Guillermina Casabona ◽  
David Neves ◽  
Yohann Couté ◽  
Félix Cicéron ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Protease Inhibitor ◽  
Rna Binding ◽  
Host Cells ◽  
Macromolecular Complex ◽  
Human Neutrophil Elastase ◽  
Host Immune System ◽  
Inner Membrane ◽  
Content Type ◽  
Α2 Macroglobulin

ABSTRACTHuman pathogens frequently use protein mimicry to manipulate host cells in order to promote their survival. Here we show that the opportunistic pathogenPseudomonas aeruginosasynthesizes a structural homolog of the human α2-macroglobulin, a large-spectrum protease inhibitor and important player of innate immunity. Small-angle X-ray scattering analysis demonstrated that the fold ofP. aeruginosaMagD (PA4489) is similar to that of the human macroglobulin and undergoes a conformational modification upon binding of human neutrophil elastase. MagD synthesis is under the control of a general virulence regulatory pathway including the inner membrane sensor RetS and the RNA-binding protein RsmA, and MagD undergoes cleavage from a 165-kDa to a 100-kDa form in all clinical isolates tested. Fractionation and immunoprecipitation experiments showed that MagD is translocated to the bacterial periplasm and resides within the inner membrane in a complex with three other molecular partners, MagA, MagB, and MagF, all of them encoded by the same six-gene genetic element. Inactivation of the whole 10-kb operon on the PAO1 genome resulted in mislocalization of uncleaved, intrans-provided MagD as well as its rapid degradation. Thus, pathogenic bacteria have acquired a homolog of human macroglobulin that plays roles in host-pathogen interactions potentially through recognition of host proteases and/or antimicrobial peptides; it is thus essential for bacterial defense.IMPORTANCEThe pathogenesis ofPseudomonas aeruginosais multifactorial and relies on surface-associated and secreted proteins with different toxic activities. Here we show that the bacterium synthesizes a 160-kDa structural homolog of the human large-spectrum protease inhibitor α2-macroglobulin. The bacterial protein is localized in the periplasm and is associated with the inner membrane through the formation of a multimolecular complex. Its synthesis is coregulated at the posttranscriptional level with other virulence determinants, suggesting that it has a role in bacterial pathogenicity and/or in defense against the host immune system. Thus, this newP. aeruginosamacromolecular complex may represent a future target for antibacterial developments.

Rat hepatic stellate cell expression of α2-macroglobulin is a feature of cellular activation: implications for matrix remodelling in hepatic fibrosis

1998 ◽  
Vol 95 (2) ◽  
pp. 179-186 ◽  
Author(s):  
C. A. KAWSER ◽  
J. P. IREDALE ◽  
P. J. WINWOOD ◽  
M. J. P. ARTHUR
Keyword(s):  
Protease Inhibitor ◽  
Hepatic Fibrosis ◽  
Hepatic Stellate Cell ◽  
Hepatic Stellate Cells ◽  
Stellate Cell ◽  
Stellate Cells ◽  
Northern Analysis ◽  
Control Value ◽  
Α2 Macroglobulin ◽  
Cell Expression

1.Hepatic stellate cells are key mediators of hepatic fibrosis. We have studied hepatic stellate cell expression of the collagenase and general protease inhibitor α2-macroglobulin after activation in tissue culture and in response to certain cytokines. 2.Hepatic stellate cells isolated by Pronase–collagenase digestion were activated by culture on uncoated plastic. By Northern analysis hepatic stellate cells undergoing activation (5 days) expressed α2-macroglobulin mRNA and α2-macroglobulin could be immunolocalized to hepatic stellate cells from 5 to 15 days of culture. 3.By ELISA of cell culture supernatants hepatic stellate cell secretion of α2-macroglobulin was found to increase from 2.78±1.13 ;ng·ml-1·μg-1 DNA per 24 ;h at 5 days of culture (n = 8) to 13.55±4.64 ;ng·ml-1·μg-1 DNA per 24 ;h at 15 days of culture (n = 7). Stimulation of hepatic stellate cells with interleukin-6 at 5 days caused a significant increase in α2-macroglobulin expression as did exposure to Kupffer-cell conditioned medium. However, exposure of hepatic stellate cells to interleukin-1, transforming growth factor-β1 and tumour necrosis factor-α had no significant effect. 4.During profibrotic liver injury plasma α2-macroglobulin levels were found to increase to between 850% and 250% of the control value (100%) after bile duct ligation (72 ;h to 13 days respectively), and to 1166% and 1106% of the control value during progressive CCl4-induced fibrosis (24 ;h to 4 weeks respectively). 5.These data suggest that hepatic stellate cells are a potential source of the potent protease inhibitor α2-macroglobulin, expression of which may inhibit matrix remodelling during progressive fibrosis.

Sign in / Sign up

Export Citation Format

Share Document