The use of monoclonal antibodies to distinguish several chemically modified forms of human α1-proteinase inhibitor

Zhu, Xiaojiu; Chan, S.K.

doi:10.1042/bj2460019

Cited by 10 publications

(6 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the structure of the El* complex is not known, there is evidence from studies utilizing antibodies that the serpin has a different conformation in the stable El* complex than when free in solution and that its structure in the stable complex resembles that of the cleaved inhibitor (Bjork et al, 1993; Zhu & Chan, 1987). In the cleaved serpin, the P2-Pi4 residues are incorporated into the A /8-sheet as the fourth strand (Loebermann et al, 1984).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Acrosin by Serpins. A Suicide Substrate Mechanism

Hermans

Monard²,

Jones³

et al. 1995

Biochemistry

View full text Add to dashboard Cite

The serpins antithrombin, protease nexin 1, and alpha 1-antitrypsin with a reactive-center arginine (Arg-alpha 1-antitrypsin) were found to inhibit the sperm protease acrosin with varying efficiency. The serpins were titrated against acrosin to determine their specific activity with respect to this enzyme. While antithrombin was fully active against acrosin, more than one molecule of Arg-alpha 1-antitrypsin and protease nexin 1 was required to inhibit one molecule of acrosin. In particular, only 2.7% of protease nexin 1 molecules interacting with acrosin formed stable complexes with the enzyme at 37 degrees C and this value decreased to 0.03% at 12 degrees C. N-terminal sequence analysis indicated that acrosin had cleaved protease nexin 1 at its reactive-center Arg-Ser bond. The results could be interpreted in terms of protease nexin 1 acting as a suicide substrate for acrosin; after the formation of an initial complex, the serpin partitioned between pathways yielding either inactivated (cleaved) serpin or a stable serpin-enzyme complex. The association rate constant (k(ass)) and inhibition constant (Ki) for the stable complexes were determined for each of the serpins by using slow-binding kinetics. The values of k(ass) were 2 x 10(5), 4 x 10(4), and 5 x 10(3) M-1 s-1 for Arg-alpha 1-antitrypsin, antithrombin, and protease nexin 1, respectively. The Ki values for the serpins were 1 nM or less. Heparin markedly accelerated the inhibition of acrosin by antithrombin and protease nexin 1; at the optimal concentration, the degree of heparin acceleration of the inhibition rate was 250- and 500-fold for antithrombin and protease nexin 1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

show abstract

Section: Discussionmentioning

confidence: 99%

Inhibition of Acrosin by Serpins. A Suicide Substrate Mechanism

Hermans

Monard²,

Jones³

et al. 1995

Biochemistry

View full text Add to dashboard Cite

show abstract

“…The membranes were incubated in Western blot detection reagent (Pierce ECL Plus Western Blotting Substrate, 32132, Thermo Fisher Scientific, Waltham, MA). Stained bands were detected using a LPR-400EX chemiluminescence imager (Taitec, Tokyo, Japan) [ 28 – 31 ].…”

Section: Methodsmentioning

confidence: 99%

Anti-FIRs (PUF60) auto-antibodies are detected in the sera of early-stage colon cancer patients

et al. 2016

View full text Add to dashboard Cite

Anti-PUF60, poly(U)-binding-splicing factor, autoantibodies are reported to be detected in the sera of dermatomyositis and Sjogren's syndrome that occasionally associated with malignancies. PUF60 is identical with far-upstream element-binding protein-interacting repressor (FIR) that is a transcriptional repressor of c-myc gene. In colorectal cancers, a splicing variant of FIR that lacks exon2 (FIRΔexon2) is overexpressed as a dominant negative form of FIR. In this study, to reveal the presence and the significance of anti-FIRs (FIR/FIRΔexon2) antibodies in cancers were explored in the sera of colorectal and other cancer patients. Anti-FIRs antibodies were surely detected in the preoperative sera of 28 colorectal cancer patients (32.2% of positive rates), and the detection rate was significantly higher than that in healthy control sera (Mann–Whitney U test, p < 0.01). The level of anti-FIRs antibodies significantly decreased after the operation (p < 0.01). Anti-FIRs antibodies were detected in the sera of early-stage and/or recurrent colon cancer patients in which anti-p53 antibodies, CEA, and CA19-9 were not detected as well as in the sera of other cancer patients. Furthermore, the area under the curve of receiver operating characteristic for anti-FIRs antibodies was significantly larger (0.85) than that for anti-p53 antibodies or CA19-9. In conclusions, the combination of anti-FIRs antibodies with other clinically available tumor markers further improved the specificity and accuracy of cancer diagnosis.

show abstract

“…The local balance between proteinases and endogenous inhibitors, such as a 1 -AT, is an important factor in determining whether inflammation results in connective tissue damage. [15][16][17][18] When the concentration of a 1 -AT in plasma falls below 0.7 mg ⁄ ml the individual is considered to have a 1 -AT deficiency. [19][20][21] The lack of circulating a 1 -AT results in uncontrolled proteolytic attack and earlyonset panacinar emphysema.…”

Section: Introductionmentioning

confidence: 99%

“…α 1 ‐AT is found in most tissues and body fluids; it is an acute‐phase reactant whose plasma concentration can rise by three‐ to four‐fold above normal (average 1.34 mg/ml) during inflammation, infection and malignant diseases. The local balance between proteinases and endogenous inhibitors, such as α 1 ‐AT, is an important factor in determining whether inflammation results in connective tissue damage 15–18 . When the concentration of α 1 ‐AT in plasma falls below 0.7 mg/ml the individual is considered to have α 1 ‐AT deficiency 19–21 .…”

Section: Introductionmentioning

confidence: 99%

Polymerized α₁‐antitrypsin is present on lung vascular endothelium. New insights into the biological significance of α₁‐antitrypsin polymerization

Aldonytė¹,

Jansson²,

Ljungberg³

et al. 2004

Histopathology

View full text Add to dashboard Cite

Polymerized alpha-antitrypsin is present on lung vascular endothelium. New insights into the biological significance of alpha-antitrypsin polymerization.Aldonyte, Ruta; Jansson, L; Ljungberg, Otto; Larsson, S; Janciauskiene, S General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Polymerized a 1 -antitrypsin is present on lung vascular endothelium. New insights into the biological significance of a 1 -antitrypsin polymerizationAims: The damage to lung tissue in chronic obstructive pulmonary disease (COPD) may involve the progressive loss of pulmonary vascular endothelial cells. Endothelial binding of a1-antitrypsin (a 1 -AT) derived from plasma has been identified, and a 1 -AT deficiency is a known genetic risk factor associated with a 1 -AT polymerization and COPD development. Therefore, in the present study we aimed to investigate if a 1 -AT is present on the lung vascular endothelium, and if it is in a polymeric form. Methods and results: Postmortem paraffin-embedded tissue specimens from 15 COPD (chronic bronchitis and emphysema) cases with and without Z a 1 -AT (Glu342Lys) deficiency and from 10 cases without signs of COPD were studied. Immunohistochemistry was performed using the streptavidin-biotin method with a monoclonal ATZ11 antibody specific for polymeric a 1 -AT, and polyclonal antibodies against human a 1 -AT and neutrophil elastase. Vascular endothelium showed intense staining for a 1 -AT with the ATZ11 antibody in all cases; however, intensity of staining in patients with a 1 -AT deficiency was greater. No endothelial staining was observed with the anti-elastase antibody.Conclusions: This is the first demonstration that a 1 -AT bound to the vascular endothelium of lungs is in a polymeric form, which also suggests a possible previously unknown role for polymeric a 1 -AT in vivo.

show abstract

The use of monoclonal antibodies to distinguish several chemically modified forms of human α1-proteinase inhibitor

Cited by 10 publications

References 18 publications

Inhibition of Acrosin by Serpins. A Suicide Substrate Mechanism

Inhibition of Acrosin by Serpins. A Suicide Substrate Mechanism

Anti-FIRs (PUF60) auto-antibodies are detected in the sera of early-stage colon cancer patients

Polymerized α₁‐antitrypsin is present on lung vascular endothelium. New insights into the biological significance of α₁‐antitrypsin polymerization

Contact Info

Product

Resources

About

The use of monoclonal antibodies to distinguish several chemically modified forms of human α1-proteinase inhibitor

Cited by 10 publications

References 18 publications

Inhibition of Acrosin by Serpins. A Suicide Substrate Mechanism

Inhibition of Acrosin by Serpins. A Suicide Substrate Mechanism

Anti-FIRs (PUF60) auto-antibodies are detected in the sera of early-stage colon cancer patients

Polymerized α1‐antitrypsin is present on lung vascular endothelium. New insights into the biological significance of α1‐antitrypsin polymerization

Contact Info

Product

Resources

About

Polymerized α₁‐antitrypsin is present on lung vascular endothelium. New insights into the biological significance of α₁‐antitrypsin polymerization