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Tytuł:
Trypsin-specific Inhibitors from the Macrolepiota procera, Armillaria mellea and Amanita phalloides wild mushrooms
Autorzy:
Lukanc, Tjaša
Brzin, Jože
Kos, Janko
Sabotič, Jerica
Powiązania:
https://bibliotekanauki.pl/articles/1038678.pdf
Data publikacji:
2017
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
basidiomycete
inhibitor
trypsin inhibitor
mushroom
trypsin
thermostable
Opis:
Wild growing mushrooms are a rich source of novel proteins with unique features. We have isolated and characterized trypsin inhibitors from two edible mushrooms, the honey fungus (Armillaria mellea) and the parasol mushroom (Macrolepiota procera), and from the poisonous death cap (Amanita phalloides). The trypsin inhibitors isolated: armespin, macrospin and amphaspin, have similar molecular masses, acidic isoelectric points and are not N-glycosylated. They are very strong trypsin inhibitors and weak chymotrypsin inhibitors. They are resistant to exposure to high temperatures and withstand extreme pH values. These exceptional characteristics are advantageous for their potential use in biotechnology, agriculture and medicine.
Źródło:
Acta Biochimica Polonica; 2017, 64, 1; 21-24
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Tadalafil alters energy metabolism in C2C12 skeletal muscle cells
Autorzy:
Sabatini, Stefania
Sgrò, Paolo
Duranti, Guglielmo
Ceci, Roberta
Di Luigi, Luigi
Powiązania:
https://bibliotekanauki.pl/articles/1039925.pdf
Data publikacji:
2011
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
phosphodiesterase type 5 inhibitor
lactate
aerobic enzymes
Opis:
Phosphodiesterases (PDEs) are a family of enzymes that hydrolyze cyclic nucleotides, thereby modulating cell functions. Three highly selective PDE5 inhibitors (PDE5i), sildenafil, vardenafil and tadalafil, have been developed for treatment of erectile dysfunction (ED). Experimental evidence showed that chronic treatment with sildenafil PDE5i in a mouse model of diet-induced obesity and insulin resistance improved insulin action and decreased circulating fatty acid levels. It has recently been shown that healthy athletes use PDE5i as performance enhancers, hence in the present study we investigated whether the long-lasting PDE5i tadalafil influences energy metabolism in C2C12 skeletal muscle cells by evaluating lactate production, glucose consumption, and citrate synthase and 3-OH acyl CoA dehydrogenase activities. Our data demonstrate that tadalafil is able to modulate energy homeostasis in mouse skeletal muscle cells, depending on the treatment length and dose.
Źródło:
Acta Biochimica Polonica; 2011, 58, 2; 237-242
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Defense against own arms: staphylococcal cysteine proteases and their inhibitors.
Autorzy:
Dubin, Grzegorz
Powiązania:
https://bibliotekanauki.pl/articles/1043443.pdf
Data publikacji:
2003
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
staphostatin
staphylococcus
ssp
proteinase
protease inhibitor
staphopain
Opis:
Staphylococcus aureus is a human pathogen causing a wide range of diseases. Most staphylococcal infections, unlike those caused by other bacteria are not toxigenic and very little is known about their pathogenesis. It has been proposed that a core of secreted proteins common to many infectious strains is responsible for colonization and infection. Among those proteins several proteases are present and over the years many different functions in the infection process have been attributed to them. However, little direct, in vivo data has been presented. Two cysteine proteases, staphopain A (ScpA) and staphopain B (SspB) are important members of this group of enzymes. Recently, two cysteine protease inhibitors, staphostatin A and staphostatin B (ScpB and SspC, respectively) were described in S. aureus shedding new light on the complexity of the processes involving the two proteases. The scope of this review is to summarize current knowledge on the network of staphylococcal cysteine proteases and their inhibitors in view of their possible role as virulence factors.
Źródło:
Acta Biochimica Polonica; 2003, 50, 3; 715-724
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Inter-α-inhibitor, hyaluronan and inflammation.
Autorzy:
Fries, Erik
Kaczmarczyk, Aneta
Powiązania:
https://bibliotekanauki.pl/articles/1043445.pdf
Data publikacji:
2003
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
inflammation
hyaluronan
TSG-6
inter-α-inhibitor
Opis:
Inter-α-inhibitor is an abundant plasma protein whose physiological function is only now beginning to be revealed. It consists of three polypeptides: two heavy chains and one light chain called bikunin. Bikunin, which has antiproteolytic activity, carries a chondroitin sulphate chain to which the heavy chains are covalently linked. The heavy chains can be transferred from inter-α-inhibitor to hyaluronan molecules and become covalently linked. This reaction seems to be mediated by TSG-6, a protein secreted by various cells upon stimulation by inflammatory cytokines. Inter-α-inhibitor has been shown to be required for the stabilization of the cumulus cell-oocyte complex during the expansion that occurs prior to ovulation. Hyaluronan-linked heavy chains in the extracellular matrix of this cellular complex have recently been shown to be tightly bound to TSG-6. Since TSG-6 binds to hyaluronan, its complex with heavy chains could stabilize the extracellular matrix by cross-linking hyaluronan molecules. Heavy chains linked to hyaluronan molecules have also been found in inflamed tissues. The physiological role of these complexes is not known but there are indications that they might protect hyaluronan against fragmentation by reactive oxygen species. TSG-6 also binds to bikunin thereby enhancing its antiplasmin activity. Taken together, these results suggest that inter-α-inhibitor is an anti-inflammatory agent which is activated by TSG-6.
Źródło:
Acta Biochimica Polonica; 2003, 50, 3; 735-742
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Evaluation of the activity of thermostable DNA polymerases in the presence of heme, as a key inhibitor in the real time PCR method in diagnostics of sepsis
Autorzy:
Gosiewski, Tomasz
Brzychczy-Włoch, Monika
Pietrzyk, Agata
Sroka, Agnieszka
Bulanda, Małgorzata
Powiązania:
https://bibliotekanauki.pl/articles/1039451.pdf
Data publikacji:
2013
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
polymerase inhibitor
heme
real time PCR
sepsis
Opis:
The study aim was evaluation of the usefulness of several thermostable DNA polymerases in real time PCR conducted in the presence of the heme. Our study had the advantage of testing several different polymerases, one of which proved to be the least sensitive to heme activity. We also found that there is no need of supplementing the reaction mixture with protective substances like BSA. Selection of the appropriate polymerase can increase the efficiency of the PCR reaction which is very important for diagnosis of sepsis and for other analyses performed on DNA template isolated from the blood.
Źródło:
Acta Biochimica Polonica; 2013, 60, 4; 603-606
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Elevation of plasma fibrinogen in silent myocardial ischaemia
Autorzy:
Grzywacz, Alina
Psuja, Piotr
Zozulińska, Maria
Elikowski, Waldemar
Zawilska, Krystyna
Powiązania:
https://bibliotekanauki.pl/articles/1044459.pdf
Data publikacji:
1999
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
silent myocardial ischaemia
fibrinogen
plasminogen activator inhibitor-1
Opis:
High plasma levels of fibrinogen and plasminogen activator inhibitor (PAI-1) are reported to be correlated with coronary heart disease. Therefore the level of fibrinogen concentration in plasma was examined and verified for the possible correlation with the previously explored PAI-1 antigen and PAI-1 activity in the pathogenesis of premature atherosclerosis (Grzywaczet al., 1998,Blood Coagul Fibrinol. 9, 245-249). Examination included only men, aged 33-46 years, who were in a stable condition for at least six months after the acute event. They were divided into two subgroups: group A (n = 14)  with and group B (n = 15) without ischaemic changes in 24 h Holter electrocardiogram. The number of involved vessels visible on the coronarography picture was similar in both groups. In the patients of group A the mean level of fibrinogen (3.92 vs 3.23 g/l, P < 0.05) was higher than in the controls (n = 15). No statistically differences were found between group B and control healthy subjects in any of the parameters measured. There were no correlation between fibrinogen concentration and PAI-1 antigen and activity levels, which were elevated in both groups of patients according to our previous study. Our results indicate that elevated levels of plasma fibrinogen and PAI-1 appeared in the group of patients with more severe disease, as revealed by silent myocardial ischaemia.
Źródło:
Acta Biochimica Polonica; 1999, 46, 4; 985-989
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
[5-(Benzyloxy)-1H-indol-1-yl]acetic acid, an aldose reductase inhibitor and PPARγ ligand
Autorzy:
Soltesova Prnova, Marta
Majekova, Magdalena
Milackova, Ivana
Díez-Dacal, Beatriz
Pérez-Sala, Dolores
Ceyhan, Muserref
Banerjee, Sreeparna
Stefek, Milan
Powiązania:
https://bibliotekanauki.pl/articles/1038997.pdf
Data publikacji:
2015
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
aldose reductase inhibitor
PPARγ ligand
diabetes
indole
Opis:
Based on overlapping structural requirements for both efficient aldose reductase inhibitors and PPAR ligands, [5-(benzyloxy)-1H-indol-1-yl]acetic acid (compound 1) was assessed for inhibition of aldose reductase and ability to interfere with PPARγ. Aldose reductase inhibition by 1 was characterized by IC50 in submicromolar and low micromolar range, for rat and human enzyme, respectively. Selectivity in relation to the closely related rat kidney aldehyde reductase was characterized by approx. factor 50. At organ level in isolated rat lenses, compound 1 significantly inhibited accumulation of sorbitol in a concentration-dependent manner. To identify crucial interactions within the enzyme binding site, molecular docking simulations were performed. Based on luciferase reporter assays, compound 1 was found to act as a ligand for PPARγ, yet with rather low activity. On balance, compound 1 is suggested as a promising lead-like scaffold for agents with the potential to interfere with multiple targets in diabetes.
Źródło:
Acta Biochimica Polonica; 2015, 62, 3; 523-528
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Structure-function relationship of serine protease-protein inhibitor interaction.
Autorzy:
Otlewski, Jacek
Jaskólski, Mariusz
Buczek, Olga
Cierpicki, Tomasz
Czapińska, Honorata
Krowarsch, Daniel
Smalas, Arne
Stachowiak, Damian
Szpineta, Agnieszka
Dadlez, Michał
Powiązania:
https://bibliotekanauki.pl/articles/1044133.pdf
Data publikacji:
2001
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
calorimetry
serine proteases
structural thermodynamics
protein inhibitor
protein-protein recognition
Opis:
We report our progress in understanding the structure-function relationship of the interaction between protein inhibitors and several serine proteases. Recently, we have determined high resolution solution structures of two inhibitors Apis mellifera chymotrypsin inhibitor-1 (AMCI-I) and Linum usitatissimum trypsin inhibitor (LUTI) in the free state and an ultra high resolution X-ray structure of BPTI. All three inhibitors, despite totally different scaffolds, contain a solvent exposed loop of similar conformation which is highly complementary to the enzyme active site. Isothermal calorimetry data show that the interaction between wild type BPTI and chymotrypsin is entropy driven and that the enthalpy component opposes complex formation. Our research is focused on extensive mutagenesis of the four positions from the protease binding loop of BPTI: P1, P1', P3, and P4. We mutated these residues to different amino acids and the variants were characterized by determination of the association constants, stability parameters and crystal structures of protease-inhibitor complexes. Accommodation of the P1 residue in the S1 pocket of four proteases: chymotrypsin, trypsin, neutrophil elastase and cathepsin G was probed with 18 P1 variants. High resolution X-ray structures of ten complexes between bovine trypsin and P1 variants of BPTI have been determined and compared with the cognate P1 Lys side chain. Mutations of the wild type Ala16 (P1') to larger side chains always caused a drop of the association constant. According to the crystal structure of the Leu16 BPTI-trypsin complex, introduction of the larger residue at the P1' position leads to steric conflicts in the vicinity of the mutation. Finally, mutations at the P4 site allowed an improvement of the association with several serine proteases involved in blood clotting. Conversely, introduction of Ser, Val, and Phe in place of Gly12 (P4) had invariably a destabilizing effect on the complex with these proteases.
Źródło:
Acta Biochimica Polonica; 2001, 48, 2; 419-428
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Some heterocyclic thione derivatives exhibit anticoccidial activity by inhibiting glycosidases
Autorzy:
Balbaa, Mahmoud
Abd El-Hady, Neama
Taha, Nabil
El Ashry, El Sayed
Powiązania:
https://bibliotekanauki.pl/articles/1039655.pdf
Data publikacji:
2012
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
inhibitor of glycosidase
anticoccidial compounds
Coccocidiosis
imidazolethione
triazolethiol
toltrazuril
Opis:
Coccidiosis is one of the most common parasitic diseases affecting many species of domestic animals. This disease has a major economic significance and the search for new compounds having anticoccidial activity is of great importance. In this article, different levels of protection from coccidian infection by Eimeria stiedae were developed in rabbits by treatment with compounds incorporating the skeleton of thiourea. These compounds include 4,5-diphenylimidazole-2-thione (1), 4,5-Diphenyl-1,2,4-triazole-3-thiol (2) and 5-(2-Hydroxyphenyl)-4-phenyl-1,2,4-triazole-3-thiol (3) compared to the anticoccidial drug toltrazuril as a reference compound. Compounds 1-3 inhibit coccidiosis-induced activity of α-glucosidase. The protection from coccidial infection by compound 1 was higher than that shown for compounds 2 and 3. These data suggest that diazole and triazole thione derivatives have a mimetic effect for anticoccidial drugs through their inhibition of glycosidases.
Źródło:
Acta Biochimica Polonica; 2012, 59, 4; 575-580
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Core structure of flavonoids precursor as an antihyperglycemic and antihyperlipidemic agent: an in vivo study in rats
Autorzy:
Najafian, Mahmoud
Ebrahim-Habibi, Azadeh
Yaghmaei, Parichehreh
Parivar, Kazem
Larijani, Bagher
Powiązania:
https://bibliotekanauki.pl/articles/1040323.pdf
Data publikacji:
2010
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
diabetes
hyperglycemia
trans-chalcone
hyperlipidemia
benzylideneacetophenone
alpha-amylase inhibitor
Opis:
trans-Chalcone is the core structure of naringenin chalcone, located halfway in the biosynthesis pathway of flavonoids. Flavonoids have been reported as mammalian alpha-amylase inhibitors, a property which could be useful in the management of postprandial hyperglycemia in diabetes and related disorders. As a mammalian alpha-amylase inhibitor in vitro, the putative beneficial effect of trans-chalcone on diabetes was tested in a streptozotocin-induced rat model of diabetes type 1, and the results analyzed with commonly used statistical methods. Significant reduction of blood glucose levels and beneficial effect on dyslipidemia were observed in diabetic rats, as well as reduction of disturbing consequences of diabetes such as high urine volume and water intake. trans-chalcone was observed to have a weight loss-inductive effect, alongside with a reduction in food intake, which is suggestive of a therapeutic potential of this compound in overweight and obese patients.
Źródło:
Acta Biochimica Polonica; 2010, 57, 4; 553-560
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
The use of serine protease from Yarrowia lipolytica yeast in the production of biopeptides from denatured egg white proteins
Autorzy:
Pokora, Marta
Zambrowicz, Aleksandra
Zabłocka, Agnieszka
Dąbrowska, Anna
Szołtysik, Marek
Babij, Konrad
Eckert, Ewelina
Trziszka, Tadeusz
Chrzanowska, Józefa
Powiązania:
https://bibliotekanauki.pl/articles/1038641.pdf
Data publikacji:
2017
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
Yarrowia lipolytica
serine protease
bioactive peptide
antioxidant
ACE-inhibitor
Opis:
Deriving non-conventional enzymes from cheaper sources than those used for commercially available enzymes may result in the production of hydrolysates with beneficial features, while drastically reducing the cost of hydrolysis. This is especially significant for enzymatic hydrolysis as a method of protein waste utilization. We have previously described the ability of non-commercial serine protease from Yarrowia lipolytica yeast to produce/release bioactive peptides from egg white protein by-products (EP). The enzymatic hydrolysis of EP was carried out for 24 h using the serine protease at an enzyme: substrate ratio of 1:30 (w/w). The obtained hydrolysate was characterized by protein degradation of 38% and also exhibited an antioxidant and cytokine-inducing activity. The isolation procedure (ultrafiltration and RP-HPLC) of bioactive peptides from the EP hydrolysate provided peptide fractions with significant antioxidant and ACE inhibitory activities. Three homogeneous and three heterogeneous peptide fractions were identified using MALDI-TOF/MS and the Mascot Search Results database. The peptides, mainly derived from ovalbumin, were composed of 2-19 amino-acid residues. We have thus demonstrated a novel ability of serine protease from Y. lipolytica to release biopeptides from an EP by-product.
Źródło:
Acta Biochimica Polonica; 2017, 64, 2; 245-253
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Fibrin D-dimer impairs the accumulation and anticoagulant properties of heparan sulphate and stimulates secretion of plasminogen activator inhibitor-1 by rabbit coronary endothelial cells.
Autorzy:
Yevdokimova, Natalia
Veselovska, Larisa
Gogolinska, Genrietta
Buchanevich, Olexandra
Kosyakova, Galina
Gritsenko, Pavel
Lugovskoj, Eduard
Komisarenko, Sergiy
Powiązania:
https://bibliotekanauki.pl/articles/1043677.pdf
Data publikacji:
2003
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
fibrin D-dimer
plasminogen activator inhibitor-1
endothelial cells
heparan sulphate
Opis:
Fibrin split product D-dimer (DD) is most probably involved in the development of vascular disorders. At 1.5 μM concentration DD inhibited the incorporation of D-[1-3H]glucosamine hydrochloride and [2-14C]acetate · Na into pericellular heparan sulphate (HS) of rabbit coronary endothelial cells without affecting other groups of glycosaminoglycans (GAGs). At the same time, DD reduced HS ability to bind antithrombin (AT) and suppressed NO production. The effect of DD on pericellular GAGs was similar to that of Nw-methyl-L-arginine, the competitive inhibitor of endothelial NO synthase (eNOS). L-Ascorbic acid, eNOS activator, increased the level of endogenous NO in the DD-treated cells, and restored HS accumulation and antithrombin binding. It is suggested that DD influence on endothelial HS may be mediated by NO production. Another effect of DD, namely, stimulation of plasminogen activator inhibitor-1 (PAI-1) secretion did not depend on the NO level. The decreased HS content, reduced anticoagulant properties of HS, and increased PAI-1 secretion disorganized the endothelial matrix, and promoted fibrin formation and vascular damage. This points to DD as an important factor in the development of vascular disorders.
Źródło:
Acta Biochimica Polonica; 2003, 50, 1; 279-289
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
New generation of peptide antibiotics
Autorzy:
Dubin, Adam
Mak, Paweł
Dubin, Grzegorz
Rzychon, Małgorzata
Stec-Niemczyk, Justyna
Wladyka, Benedykt
Maziarka, Katarzyna
Chmiel, Dorota
Powiązania:
https://bibliotekanauki.pl/articles/1041366.pdf
Data publikacji:
2005
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
staphostatin
Staphylococcus
virulence factor
hemoglobin
protease inhibitor
hemocidins
antimicrobial agents
antibiotics
Opis:
The increasing antibiotic resistance of pathogenic bacteria calls for the development of alternative antimicrobial strategies. Possible approaches include the development of novel, broad-spectrum antibiotics as well as specific targeting of individual bacterial virulence factors. It is impossible to decide currently which strategy will prove more successful in the future since they both promise different advantages, but also introduce diverse problems. Considering both approaches, our laboratory's research focuses on the evaluation of hemocidins, broad-spectrum antibacterial peptides derived from hemoglobin and myoglobin, and staphostatins, specific inhibitors of staphopains - Staphylococcus aureus secreted proteases that are virulence factors regarded as possible targets for therapy. The article summarizes recent advances in both fields of study and presents perspectives for further development and possible applications.
Źródło:
Acta Biochimica Polonica; 2005, 52, 3; 633-638
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Role of anti-apoptotic pathways activated by BCR/ABL in the resistance of chronic myeloid leukemia cells to tyrosine kinase inhibitors
Autorzy:
Danisz, Katarzyna
Blasiak, Janusz
Powiązania:
https://bibliotekanauki.pl/articles/1039432.pdf
Data publikacji:
2013
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
BCR/ABL
chronic myeloid leukemia
apoptotic signaling
tyrosine kinase inhibitor
imatinib
drug resistance
Opis:
Chronic myeloid leukemia (CML) is a hematological stem cell disorder characterized by the excessive proliferation of the myeloid lineage. In its initial chronic phase, the myeloid progenitor cells expand and demonstrate apparently normal differentiation. The disease may then transform into the accelerated phase, usually associated with resistance to therapy, and finally, into acute leukemic progression phase - blast crisis. Abnormal myeloid cells produce progenitors, which have lost their ability to differentiate, but retain the capacity to proliferate. The molecular hallmark of CML is the Philadelphia chromosome, resulting from reciprocal chromosome translocation, t(9;22)(q34;q11), and containing the BCR/ABL fusion gene, producing the BCR/ABL protein with a constitutive tyrosine kinase activity. BCR/ABL-positive cells have faster growth and proliferation over their normal counterparts and are resistant to apoptosis. Introduction of imatinib (IM), a tyrosine kinase inhibitor, revolutionized the therapy of CML, changing it from a fatal disease into a chronic disorder. However, some patients show a primary resistance to IM, others acquire such resistance in the course of therapy. Therefore, a small number of leukemic stem cells retains self-renewal capacity under IM treatment. Because BCR/ABL is involved in many signaling pathways, some of them may be essential for resistance to IM-induced apoptosis. The PI3K/AKT, Ras and JAK/STAT signaling pathways are involved in resistance to apoptosis and can be activated by BCR/ABL. Therefore, they can be candidates for BCR/ABL-dependent pro-survival pathway(s), allowing a fraction of CML cells to withstand treatment with tyrosine kinase inhibitors.
Źródło:
Acta Biochimica Polonica; 2013, 60, 4; 503-514
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Inactivation of α1-proteinase inhibitor by Candida albicans aspartic proteases favors the epithelial and endothelial cell colonization in the presence of neutrophil extracellular traps
Autorzy:
Gogol, Mariusz
Ostrowska, Dominika
Klaga, Kinga
Bochenska, Oliwia
Wolak, Natalia
Aoki, Wataru
Ueda, Mitsuyoshi
Kozik, Andrzej
Rapala-Kozik, Maria
Powiązania:
https://bibliotekanauki.pl/articles/1038860.pdf
Data publikacji:
2016
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
Candida albicans
aspartic proteases
α1-proteinase inhibitor
elastase
neutrophil extracellular traps
inflammation
Opis:
Candida albicans, a causative agent of opportunistic fungal infections in immunocompromised patients, uses ten secreted aspartic proteases (SAPs) to deregulate the homeostasis of the host organism on many levels. One of these deregulation mechanisms involves a SAP-dependent disturbance of the control over proteolytic enzymes of the host by a system of dedicated proteinase inhibitors, with one important example being the neutrophil elastase and alpha1-proteinase inhibitor (A1PI). In this study, we found that soluble SAPs 1-4 and the cell membrane-anchored SAP9 efficiently cleaved A1PI, with the major cleavage points located at the C-terminal part of A1PI in a close vicinity to the reactive-site loop that plays a critical role in the inhibition mechanism. Elastase is released by neutrophils to the environment during fungal infection through two major processes, a degranulation or formation of neutrophil extracellular traps (NET). Both, free and NET-embedded elastase forms, were found to be controlled by A1PI. A local acidosis, resulting from the neutrophil activity at the infection sites, favors A1PI degradation by SAPs. The deregulation of NET-connected elastase affected a NET-dependent damage of epithelial and endothelial cells, resulting in the increased susceptibility of these host cells to candidal colonization. Moreover, the SAP-catalyzed cleavage of A1PI was found to decrease its binding affinity to a proinflammatory cytokine, interleukin-8. The findings presented here suggest a novel strategy used by C. albicans for the colonization of host tissues and overcoming the host defense.
Źródło:
Acta Biochimica Polonica; 2016, 63, 1; 167-175
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
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