Carboxypeptidase‐B activation peptide, a marker of pancreatic acinar injury, but not <scp>l</scp>‐selectin, a marker of neutrophil activation, predicts severity of acute pancreatitis

Hilal, Mohammed Abu; Ung, Christopher; Westlake, Sarah; Johnson, C. D.

doi:10.1111/j.1440-1746.2006.04550.x

Cited by 15 publications

(5 citation statements)

References 43 publications

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“…The levels of E-selectin and P-selectin are elevated in severe AP and, thus, may be biomarkers of AP severity [ 14 , 60 – 63 ]; in contrast, the L-selectin level is not correlated with the severity of AP [ 14 , 64 , 65 ]. Elevated E- and/or P-selectin levels were correlated with a higher mortality rate, longer hospitalization, and development of pancreatic necrosis [ 60 , 61 ].…”

Section: Introductionmentioning

confidence: 99%

Adhesion molecules and pancreatitis

2018

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Acute and chronic pancreatitises are gastrointestinal inflammatory diseases, the incidence of which is increasing worldwide. Most (~ 80%) acute pancreatitis (AP) patients have mild disease, and about 20% have severe disease, which causes multiple organ failure and has a high mortality rate. Chronic pancreatitis (CP) is characterized by chronic inflammation and destruction of normal pancreatic parenchyma, which leads to loss of exocrine and endocrine tissues. Patients with CP also have a higher incidence of pancreatic ductal adenocarcinoma. Although a number of factors are associated with the development and progression of AP and CP, the underlying mechanism is unclear. Adhesion molecules play important roles in cell migration, proliferation, and signal transduction, as well as in development and tissue repair. Loosening of cell-cell adhesion between pancreatic acinar cells and/or endothelial cells increases solute permeability, resulting in interstitial edema, which promotes inflammatory cell migration and disrupts tissue structure. Oxidative stress, which is one of the important pathogenesis of pancreatitis, leads to upregulation of adhesion molecules. Soluble adhesion molecules are reportedly involved in AP. In this review, we focus on the roles of tight junctions (occludin, tricellulin, claudin, junctional adhesion molecule, and zonula occludin), adherens junctions (E-cadherin and p120-, α-, and β-catenin), and other adhesion molecules (selectin and intercellular adhesion molecules) in the progression of AP and CP. Maintaining the normal function of adhesion molecules and preventing their abnormal activation maintain the structure of the pancreas and prevent the development of pancreatitis.

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Section: Introductionmentioning

confidence: 99%

Adhesion molecules and pancreatitis

2018

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“…In other compartments of the body, different CPs participate in tightly regulated processes such as, for instance, the maturation of physiologically active peptide hormones. Moreover, M14 peptidases are therapeutically interesting molecules because of their involvement in acute pancreatitis [9–11], cancer [12–14], diabetes [15, 16], fibrinolysis [17], and inflammation [18]. …”

Section: Introductionmentioning

confidence: 99%

Structural and Functional Analysis of the Complex between Citrate and the Zinc Peptidase Carboxypeptidase A

et al. 2011

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A high-resolution carboxypeptidase-Zn2+-citrate complex was studied by X-ray diffraction and enzyme kinetics for the first time. The citrate molecule acts as a competitive inhibitor of this benchmark zinc-dependent peptidase, chelating the catalytic zinc ion in the active site of the enzyme and inducing a conformational change such that carboxypeptidase adopts the conformation expected to occur by substrate binding. Citrate adopts an extended conformation with half of the molecule facing the zinc ion, while the other half is docked in the S1′ hydrophobic specificity pocket of the enzyme, in contrast with the binding mode expected for a substrate like phenylalanine or a peptidomimetic inhibitor like benzylsuccinic acid. Combined structural and enzymatic analysis describes the characteristics of the binding of this ligand that, acting against physiologically relevant zinc-dependent proteases, may serve as a general model in the design of new drug-protecting molecules for the oral delivery of drugs of peptide origin.

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“…CPB1 is the more stable tissue isoform of the carboxypeptidase B family and is found in elevated levels in acute pancreatitis16,39. Metallocarboxypeptidases (MCPs), especially those which belong to the carboxypeptidase B subfamily, are known to regulate inflammation39,40.…”

Section: Discussionmentioning

confidence: 99%

Immuno-spin trapping of a post-translational carboxypeptidase B1 radical formed by a dual role of xanthine oxidase and endothelial nitric oxide synthase in acute septic mice

Chatterjee

Ehrenshaft

Bhattacharjee

et al. 2009

Free Radical Biology and Medicine

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Post-translational modification of proteins due to exposure to radicals and other reactive species are markers of metabolic and inflammatory oxidative stress such as sepsis. This study uses the nitrone spin-trap DMPO and a combination of immuno-spin trapping and mass spectrometry to identify in vivo products of radical reactions in mice. We report the detection of dose-dependent production of DMPO-carboxypeptidase B1 (CPB1) adducts in the spleen of mice treated with lipopolysaccharide (LPS). Additionally, we report significant detection of DMPO-CPB1 adducts in mice experiencing normal physiological conditions. Treatments with inhibitors and experiments with knock-out mice indicate that xanthine oxidase and endothelial nitric oxide synthase are important sources of the reactive species that lead to CPB1 adduct formation. We also report a significant loss of CPB1 activity following LPS challenge in conjunction with an increase in CPB1 protein accumulation. This suggests the presence of a possible mechanism for CPB1 activity loss with compensatory protein production.

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Carboxypeptidase‐B activation peptide, a marker of pancreatic acinar injury, but not l‐selectin, a marker of neutrophil activation, predicts severity of acute pancreatitis

Cited by 15 publications

References 43 publications

Adhesion molecules and pancreatitis

Adhesion molecules and pancreatitis

Structural and Functional Analysis of the Complex between Citrate and the Zinc Peptidase Carboxypeptidase A

Immuno-spin trapping of a post-translational carboxypeptidase B1 radical formed by a dual role of xanthine oxidase and endothelial nitric oxide synthase in acute septic mice

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