Serine proteases in the extracellular preparations of Phytophthora infestans: does their presence relate to the aggressiveness of the pathogen?

In this study the aggressiveness of nine isolates of P. infestans was determined using detached leaflets from cultivars Bintje and Stirling. The growth of the isolates on the leaflets was recorded on a daily basis, for seven days, and an assessment of their aggressiveness could then be made. Extracellular preparations (ECPs) from the zoospore suspension of each isolate were used as a source of proteolytic activity. The ECPs were found to contain a level of serine protease activity using BTEE (N-Benzoyl-L-Tyrosine Ethyl Ester) as a substrate and recording the absorbance at 256 nm. The possible relationship between the serine protease activity and the aggressiveness of the isolate is discussed.

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Multifaceted Analyses of Epidermal Serine Protease Activity in Patients with Atopic Dermatitis

International Journal of Molecular Sciences ◽

10.3390/ijms21030913 ◽

2020 ◽

Vol 21 (3) ◽

pp. 913 ◽

Cited By ~ 1

Author(s):

Hayato Nomura ◽

Mutsumi Suganuma ◽

Takuya Takeichi ◽

Michihiro Kono ◽

Yuki Isokane ◽

...

Keyword(s):

Atopic Dermatitis ◽

Serine Protease ◽

Protease Activity ◽

Serine Proteases ◽

Immunoglobulin E ◽

Total Serum ◽

Tape Stripping ◽

Blood Eosinophil ◽

Peripheral Blood Eosinophil ◽

Serine Protease Activity

The serine proteases kallikrein-related peptidase (KLK) 5 and KLK7 cleave cell adhesion molecules in the epidermis. Aberrant epidermal serine protease activity is thought to play an important role in the pathogenesis of atopic dermatitis (AD). We collected the stratum corneum (SC) from healthy individuals (n = 46) and AD patients (n = 63) by tape stripping and then measuring the trypsin- and chymotrypsin-like serine protease activity. We also analyzed the p.D386N and p.E420K of SPINK5 variants and loss-of-function mutations of FLG in the AD patients. The serine protease activity in the SC was increased not only in AD lesions but also in non-lesions of AD patients. We found, generally, that there was a positive correlation between the serine protease activity in the SC and the total serum immunoglobulin E (IgE) levels, serum thymus and activation-regulated chemokine (TARC) levels, and peripheral blood eosinophil counts. Moreover, the p.D386N or p.E420K in SPINK5 and FLG mutations were not significantly associated with the SC’s serine protease activity. Epidermal serine protease activity was increased even in non-lesions of AD patients. Such activity was found to correlate with a number of biomarkers of AD. Further investigations of serine proteases might provide new treatments and prophylaxis for AD.

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Protean proteases: at the cutting edge of lung diseases

European Respiratory Journal ◽

10.1183/13993003.01200-2015 ◽

2017 ◽

Vol 49 (2) ◽

pp. 1501200 ◽

Cited By ~ 28

Author(s):

Clifford Taggart ◽

Marcus A. Mall ◽

Gilles Lalmanach ◽

Didier Cataldo ◽

Andreas Ludwig ◽

...

Keyword(s):

Protease Inhibitor ◽

Serine Protease ◽

Protease Activity ◽

Serine Proteases ◽

Lung Diseases ◽

Serine Protease Inhibitor ◽

Matrix Metalloproteases ◽

Integrative Biology ◽

Therapeutic Tool ◽

Serine Protease Activity

Proteases were traditionally viewed as mere protein-degrading enzymes with a very restricted spectrum of substrates. A major expansion in protease research has uncovered a variety of novel substrates, and it is now evident that proteases are critical pleiotropic actors orchestrating pathophysiological processes. Recent findings evidenced that the net proteolytic activity also relies upon interconnections between different protease and protease inhibitor families in the protease web.In this review, we provide an overview of these novel concepts with a particular focus on pulmonary pathophysiology. We describe the emerging roles of several protease families including cysteine and serine proteases.The complexity of the protease web is exemplified in the light of multidimensional regulation of serine protease activity by matrix metalloproteases through cognate serine protease inhibitor processing. Finally, we will highlight how deregulated protease activity during pulmonary pathogenesis may be exploited for diagnosis/prognosis purposes, and utilised as a therapeutic tool using nanotechnologies.Considering proteases as part of an integrative biology perspective may pave the way for the development of new therapeutic targets to treat pulmonary diseases related to intrinsic protease deregulation.

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Overhydration Measured by Bioimpedance Spectroscopy and Urinary Serine Protease Activity Are Risk Factors for Progression of Chronic Kidney Disease

Kidney & Blood Pressure Research ◽

10.1159/000510649 ◽

2020 ◽

Vol 45 (6) ◽

pp. 955-968

Author(s):

Anja Schork ◽

Bernhard N. Bohnert ◽

Nils Heyne ◽

Andreas L. Birkenfeld ◽

Ferruh Artunc

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Serine Protease ◽

Protease Activity ◽

Serine Proteases ◽

Cox Regression ◽

Bioimpedance Spectroscopy ◽

Operating Characteristics ◽

Cutoff Values ◽

Serine Protease Activity

Background: Overhydration (OH) is common in chronic kidney disease (CKD) and might be related to the excretion of urinary serine proteases. Progression of CKD is associated with proteinuria; however, the interrelations of urinary serine proteases, OH, and progression of CKD remain unclear. Methods: In n = 179 patients with stable nondialysis-dependent CKD of all stages, OH was measured using bioimpedance spectroscopy (Body Composition Monitor; Fresenius), and urinary serine protease activity was determined using the peptide substrate S-2302. After a median follow-up of 5.9 (IQR: 3.9–6.5) years, progression to end-stage renal disease (ESRD) was analyzed retrospectively. Results: OH correlated with baseline MDRD-eGFR, urinary albumin creatinine ratio (ACR), and urinary aprotinin-sensitive serine protease activity. Progression to ESRD occurred in n = 33 patients (19%) and correlated with OH and urinary serine protease activity as well as MDRD-eGFR and ACR. Patients were divided into 2 groups determined by cutoff values from receiver operating characteristics for MDRD-eGFR (32 mL/min/1.73 m2), ACR (43 mg/g creatinine), urinary serine protease activity (0.9 RU/g creatinine), and OH (1 L/1.73 m2). Across these cutoff values, Kaplan-Meier curves for renal survival showed significant separations of the groups. In Cox regression adjusted for MDRD-eGFR, ACR, P-NT-pro-BNP, systolic blood pressure, and diabetes mellitus, patients with OH >1 L/1.73 m2 had a 3.32 (95% CI: 1.26–8.76)-fold higher risk for progression to ESRD. Conclusions: Our results corroborate that OH detected by bioimpedance spectroscopy in CKD patients is an independent risk factor for progression to ESRD in addition to GFR and albuminuria. Urinary serine protease activity is associated with OH and progression of CKD and provides a possible underlying mechanism.

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Characterisation of the effects on proteases of Heterodera glycines and Meloidogyne incognita second-stage juveniles by inhibitors obtained from cysts of H. glycines

Nematology ◽

10.1163/15685411-00003151 ◽

2018 ◽

Vol 20 (5) ◽

pp. 461-470

Author(s):

Edward P. Masler

Keyword(s):

Serine Protease ◽

Meloidogyne Incognita ◽

Protease Activity ◽

Serine Proteases ◽

Heterodera Glycines ◽

Nematode Species ◽

Protease Inhibition ◽

Second Stage ◽

Egg Extract ◽

Serine Protease Activity

Summary The protease inhibitor component of Heterodera glycines cyst contents was explored using a battery of peptide substrates and H. glycines and Meloidogyne incognita second-stage juveniles as enzyme sources. Protease inhibitors were prepared by heat-denaturing H. glycines cyst-egg extract (hHglCE), which was used in all inhibition exploration. Eight substrates targeting four endoprotease groups (aspartic, cysteine, metallo- and serine proteases) revealed that protease inhibition by hHglCE varied significantly between H. glycines and M. incognita with seven of the eight substrates. Only cysteine protease activity was inhibited equally between H. glycines and M. incognita. Aspartic protease activity was inhibited more strongly in H. glycines and serine protease activity was inhibited more strongly in M. incognita. Digestion of five matrix metalloprotease (MMP) substrates was inhibited more strongly in H. glycines (two substrates) and M. incognita (three substrates). These variations were particularly intriguing given the potential association of MMP proteases with developing embryos. Inhibition of digestion of nematode FMRFamide-like peptides (FLPs) showed less variation between nematode species than the targeted substrates, but inhibition did vary significantly across substrates within each species. Digestion of FLP-6 was the least affected by hHglCE but was inhibited significantly more in M. incognita than in H. glycines. Residue differences between two FLP-14 sequences significantly affected inhibition of FLP-14 digestion in both H. glycines and M. incognita. RP-HPLC fractionation of hHglCE clearly demonstrated the presence of high (Fr No.5) and low (Fr No.14) polarity inhibitor components. Potency of inhibition of M. incognita serine protease activity, based upon IC50 values (1.68 and 2.78 hHglCEeq reaction−1 for Fr No.5 and Fr No.14, respectively), was reduced significantly from unfractionated hHglCE (IC50 = 0.61), suggesting inhibitor dilution, loss of component synergy, or both, due to fractionation.

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Evidence that cell surface localization of serine protease activity facilitates cleavage of the protease activated receptor CDCP1

Biological Chemistry ◽

10.1515/hsz-2017-0308 ◽

2018 ◽

Vol 399 (9) ◽

pp. 1091-1097

Author(s):

Yaowu He ◽

Janet C. Reid ◽

Hui He ◽

Brittney S. Harrington ◽

Brittney Finlayson ◽

...

Keyword(s):

Serine Protease ◽

Protease Activity ◽

Serine Proteases ◽

Membrane Localization ◽

Cub Domain ◽

Serine Protease Activity ◽

Surface Localization ◽

Cell Surface Localization

Abstract The cellular receptor CUB domain containing protein 1 (CDCP1) is commonly elevated and functionally important in a range of cancers. CDCP1 is cleaved by serine proteases at adjacent sites, arginine 368 (R368) and lysine 369 (K369), which induces cell migration in vitro and metastasis in vivo. We demonstrate that membrane localization of serine protease activity increases efficacy of cleavage of CDCP1, and that both secreted and membrane anchored serine proteases can have distinct preferences for cleaving at CDCP1-R368 and CDCP1-K369. Approaches that disrupt membrane localization of CDCP1 cleaving serine proteases may interfere with the cancer promoting effects of CDCP1 proteolysis.

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Colonic luminal serine-protease activity: a pathophysiological factor in diarrhea-predominant irritable bowel syndrome

Zeitschrift für Gastroenterologie ◽

10.1055/s-2007-982657 ◽

2007 ◽

Vol 45 (05) ◽

Author(s):

K Gecse ◽

R Róka ◽

A Rosztóczy ◽

F Izbéki ◽

L Ferrier ◽

...

Keyword(s):

Irritable Bowel Syndrome ◽

Serine Protease ◽

Protease Activity ◽

Serine Protease Activity ◽

Irritable Bowel

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Faculty Opinions recommendation of HtrA2 promotes cell death through its serine protease activity and its ability to antagonize inhibitor of apoptosis proteins.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1003672.38258 ◽

2002 ◽

Author(s):

John Abrams

Keyword(s):

Cell Death ◽

Serine Protease ◽

Protease Activity ◽

Inhibitor Of Apoptosis ◽

Inhibitor Of Apoptosis Proteins ◽

Serine Protease Activity ◽

Apoptosis Proteins

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A novel mechanism for imatinib mesylate–induced cell death of BCR-ABL–positive human leukemic cells: caspase-independent, necrosis-like programmed cell death mediated by serine protease activity

Blood ◽

10.1182/blood-2003-05-1605 ◽

2004 ◽

Vol 103 (6) ◽

pp. 2299-2307 ◽

Cited By ~ 73

Author(s):

Masayuki Okada ◽

Souichi Adachi ◽

Tsuyoshi Imai ◽

Ken-ichiro Watanabe ◽

Shin-ya Toyokuni ◽

...

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Serine Protease ◽

Imatinib Mesylate ◽

Protease Activity ◽

Kinase Inhibitor ◽

Leukemic Cells ◽

Endonuclease G ◽

Serine Protease Activity ◽

Human Leukemic Cells

Abstract Caspase-independent programmed cell death can exhibit either an apoptosis-like or a necrosis-like morphology. The ABL kinase inhibitor, imatinib mesylate, has been reported to induce apoptosis of BCR-ABL–positive cells in a caspase-dependent fashion. We investigated whether caspases alone were the mediators of imatinib mesylate–induced cell death. In contrast to previous reports, we found that a broad caspase inhibitor, zVAD-fmk, failed to prevent the death of imatinib mesylate–treated BCR-ABL–positive human leukemic cells. Moreover, zVAD-fmk–preincubated, imatinib mesylate–treated cells exhibited a necrosis-like morphology characterized by cellular pyknosis, cytoplasmic vacuolization, and the absence of nuclear signs of apoptosis. These cells manifested a loss of the mitochondrial transmembrane potential, indicating the mitochondrial involvement in this caspase-independent necrosis. We excluded the participation of several mitochondrial factors possibly involved in caspase-independent cell death such as apoptosis-inducing factor, endonuclease G, and reactive oxygen species. However, we observed the mitochondrial release of the serine protease Omi/HtrA2 into the cytosol of the cells treated with imatinib mesylate or zVAD-fmk plus imatinib mesylate. Furthermore, serine protease inhibitors prevented the caspase-independent necrosis. Taken together, our results suggest that imatinib mesylate induces a caspase-independent, necrosis-like programmed cell death mediated by the serine protease activity of Omi/HtrA2.

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