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Kallikrein

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https://www.readbyqxmd.com/read/28636767/aberrant-expression-of-kallikrein-related-peptidase-7-is-correlated-to-human-melanoma-aggressiveness-by-stimulating-cell-migration-and-invasion
#1
Tiphaine Delaunay, Lydia Deschamps, Meriem Haddada, Francine Walker, Antoninus Soosaipillai, Feryel Soualmia, Chahrazade El Amri, Eleftherios P Diamandis, Maria Brattsand, Viktor Magdolen, Dalila Darmoul
Members of the tissue kallikrein-related peptidase (KLK) family not only regulate several important physiological functions, but aberrant expression has also been associated with various malignancies. Clinically, KLKs have been suggested as promising biomarkers for diagnosis and prognosis in many types of cancer. As of yet, expression of KLKs and their role in skin cancers are, however, poorly addressed. Malignant melanoma is an aggressive disease associated with poor prognosis. Hence, diagnostic biomarkers to monitor melanoma progression are needed...
June 21, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28636578/human-neuropsin-gene-in-depression
#2
Kinga Bobińska, Joanna Mossakowska-Wójcik, Janusz Szemraj, Piotr Gałecki, Marlena Zajączkowska, Monika Talarowska
BACKGROUND: Neuropsin (NP, kallikrein 8, KLK8) - a kallikrein gene-related (KLK) endoprotease - plays a key role in neuroplasticity processes, since intracellular signal cascades and regulation of gene expression are engaged in long-term synaptic plasticity. The main aim of this paper is to compare expression of the human neuropsin gene on the mRNA level in a group of patients diagnosed with depression and in a group of healthy subjects who have never been treated psychiatrically. SUBJECTS AND METHODS: 291 people, aged 18-67, were qualified to participate in the experiment: major recurrent depression group (MRD) and the control group (CG)...
June 2017: Psychiatria Danubina
https://www.readbyqxmd.com/read/28632925/a-kallikrein-targeting-rna-aptamer-inhibits-the-intrinsic-pathway-of-coagulation-and-reduces-bradykinin-release
#3
K-A Steen-Burrell, J Layzer, B A Sullenger
BACKGROUND: Plasma kallikrein is a serine protease that plays an integral role in many biological processes including coagulation, inflammation, and fibrinolysis. The main function of kallikrein in coagulation is the amplification of activated factor XIIa (FXIIa) generation which ultimately leads to thrombin generation and fibrin clot formation. Kallikrein is generated by FXIIa-mediated cleavage of the zymogen, prekallikrein which is usually complexed with the nonenzymatic cofactor, high-molecular-weight kininogen (HK)...
June 20, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28621557/a-positive-association-between-the-human-tissue-kallikerin-gene-a2233c-polymorphism-and-blood-pressure-response-to-benazepril
#4
Zhe Hong, Liying Pan, Jiali Fei, Zhangqing Ma, Zongyuan Hong
BACKGROUND: It is generally believed that essential hypertension is influenced by both genetic and environmental factors, as well as their interactions. Tissue kallikrein encoded by the tissue kallikrein gene (KLK1) is a key serine proteinase of kallikrein-kinin system, which is capable of generating potent vasactive peptides, kinins, by selective cleavage of the kininogen substrate. It was reported that the A2233 → C polymorphism in KLK1 gene is associated with essential hypertension...
June 16, 2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/28615200/kallikrein-related-peptidase-5-contributes-to-h3n2-influenza-virus-infection-in-human-lungs
#5
Melia Magnen, Fabien Gueugnon, Antoine Guillon, Thomas Baranek, Virginie C Thibault, Agnès Petit-Courty, Simon J de Veer, Jonathan Harris, Alison A Humbles, Mustapha Si-Tahar, Yves Courty
The HA (hemagglutinin) of influenza virus must be activated by proteolysis before the virus can become infectious. Previous studies have indicated that HA cleavage is driven by membrane-bound or extracellular serine proteases in the respiratory tract. However, there is still uncertainty as to which proteases are critical for activating the HA of seasonal influenza A viruses (IAV) in humans. This study focuses on human KLK1 and KLK5, two of the 15 serine proteases known as the kallikrein-related peptidases (KLK)...
June 14, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28615126/unveiling-the-participation-of-avian-kinin-ornithokinin-and-its-receptors-in-the-chicken-inflammatory-response
#6
Rodrigo Guabiraba, Damien Garrido, Geoffrey Bailleul, Angélina Trotereau, Mélanie Pinaud, Anne-Christine Lalmanach, Nathalie K Chanteloup, Catherine Schouler
Vasoactive peptides are key early mediators of inflammation released through activation of different enzymatic systems. The mammalian kinin-kallikrein (K-KLK) system produces bradykinin (BK) through proteolytic cleavage of a kininogen precursor by enzymes named kallikreins. BK acts through specific ubiquitous G-protein coupled receptors (B1R and B2R) to participate in physiological processes and inflammatory responses, such as activation of mononuclear phagocytes. In chickens, the BK-like nonapeptide ornithokinin (OK) has been shown to promote intracellular calcium increase in embryonic fibroblasts and to be vasodilatory in vivo...
June 2017: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/28611678/a-fourth-klk4-mutation-is-associated-with-enamel-hypomineralisation-and-structural-abnormalities
#7
Claire E L Smith, Jennifer Kirkham, Peter F Day, Francesca Soldani, Esther J McDerra, James A Poulter, Christopher F Inglehearn, Alan J Mighell, Steven J Brookes
"Amelogenesis imperfecta" (AI) describes a group of genetic conditions that result in defects in tooth enamel formation. Mutations in many genes are known to cause AI, including the gene encoding the serine protease, kallikrein related peptidase 4 (KLK4), expressed during the maturation stage of amelogenesis. In this study we report the fourth KLK4 mutation to be identified in autosomal recessively-inherited hypomaturation type AI, c.632delT, p.(L211Rfs(*)37) (NM_004917.4, NP_004908.4). This homozygous variant was identified in five Pakistani AI families and is predicted to result in a transcript with a premature stop codon that escapes nonsense mediated decay...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28609548/inhibitors-of-kallikrein-related-peptidases-an-overview
#8
REVIEW
Nicolas Masurier, Dominique P Arama, Chahrazade El Amri, Vincent Lisowski
Kallikrein-related peptidases (KLKs) are a family of 15 secreted serine proteases that are involved in various physiological processes. Their activities are subtly regulated by various endogenous inhibitors, ranging from metallic ions to macromolecular entities such as proteins. Furthermore, dysregulation of KLK activity has been linked to several pathologies, including cancer and skin and inflammatory diseases, explaining the numerous efforts to develop KLK-specific pharmacological inhibitors as potential therapeutic agents...
June 13, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28604413/single-chain-factor-xii-a-new-form-of-activated-factor-xii
#9
Ivan Ivanov, Anton Matafonov, David Gailani
PURPOSE OF REVIEW: Exposure of blood to foreign surfaces induces reciprocal conversion of the plasma proteins factor XII (fXII) and plasma prekallikrein (PPK) to the proteases α-fXIIa and α-kallikrein. This process, called contact activation, has a range of effects on host defence mechanisms, including promoting coagulation. The nature of the triggering mechanism for contact activation is debated. One hypothesis predicts that fXII has protease activity, either intrinsically or upon surface-binding, that initiates contact activation...
June 9, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28601761/improving-virtual-screening-predictive-accuracy-of-human-kallikrein-5-inhibitors-using-machine-learning-models
#10
Xingang Fang, Sikha Bagui, Subhash Bagui
The readily available high throughput screening (HTS) data from the PubChem database provides an opportunity for mining of small molecules in a variety of biological systems using machine learning techniques. From the thousands of available molecular descriptors developed to encode useful chemical information representing the characteristics of molecules, descriptor selection is an essential step in building an optimal quantitative structural-activity relationship (QSAR) model. For the development of a systematic descriptor selection strategy, we need the understanding of the relationship between: (i) the descriptor selection; (ii) the choice of the machine learning model; and (iii) the characteristics of the target bio-molecule...
May 29, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28592188/polymer-coated-cardiopulmonary-bypass-circuit-attenuates-upregulation-of-both-proteases-protease-inhibitors-and-platelet-degranulation-in-pigs
#11
Shoichi Suehiro, Kouji Shimizu, Kensuke Imai, Atsushi Niii, Kazuhiro Akeho, Hayato Nakata, Akane Yamaguchi, Ken-Ichi Matsumoto, Teiji Oda
INTRODUCTION: Interaction of blood with a cardiopulmonary bypass (CPB) circuit activates the coagulation-fibrinolysis, complement and kinin-kallikrein systems that are mainly supported by proteases and their inhibitors. METHODS: Biocompatibility of a new polymer-coated (SEC-coated) CPB circuit was globally evaluated and compared with that of a non-coated CPB circuit by quantitative proteomics, using isobaric tags for relative and absolute quantification labeling tandem mass spectrometry...
June 1, 2017: Perfusion
https://www.readbyqxmd.com/read/28573254/structural-characteristics-and-antihypertensive-effects-of-angiotensin-i-converting-enzyme-inhibitory-peptides-in-the-renin-angiotensin-and-kallikrein-kinin-systems
#12
Sivananthan Manoharan, Adawiyah Suriza Shuib, Noorlidah Abdullah
BACKGROUND: The commercially available synthetic angiotensin-I-converting enzyme (ACE) inhibitors are known to exert negative side effects which have driven many research groups globally to discover the novel ACE inhibitors. METHOD: Literature search was performed within the PubMed, ScienceDirect.com and Google Scholar. RESULTS: The presence of proline at the C-terminal tripeptide of ACE inhibitor can competitively inhibit the ACE activity...
2017: African Journal of Traditional, Complementary, and Alternative Medicines: AJTCAM
https://www.readbyqxmd.com/read/28570146/recombinant-c1-esterase-inhibitor-reduces-cytokine-storm-in-an-ex-vivo-whole-blood-model
#13
Vladimir A Bobkov, Roman V Tikhonov, Alexander M Shuster, Dmitry A Poteryaev, Veronika N Bade
C1 esterase inhibitor (C1INH) is an abundant component of blood plasma (the average concentration is 250 mg/L); it is known to be involved in several biological processes, for instance, in the regulation of the coagulation system, adhesion of leukocytes on endothelial cells, and in the regulation of complement and kallikrein cascades. Lately, the role of C1INH in immunomodulation has gained considerable attention. We used an ex vivo whole blood model to examine the influence of C1INH and its mutated variants on the inflammatory cytokines interleukin (IL)-6, tumor necrosis factor-α (TNFα), and IL-1β...
June 1, 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/28559305/biochemical-and-functional-characterization-of-the-human-tissue-kallikrein-9
#14
Panagiota S Filippou, Sofia Farkona, Davor Brinc, Yijing Yu, Ioannis Prassas, Eleftherios P Diamandis
Human tissue kallikrein 9 (KLK9) is a member of the kallikrein-related family of proteases. Despite its known expression profile, much less is known about the functional roles of this protease and its implications in normal physiology and disease. We present here the first data on the biochemical characterization of KLK9, investigate parameters that affect its enzymatic activity (such as inhibitors) and provide preliminary insights into its putative substrates. We show that mature KLK9 (mat-KLK9) is a glycosylated chymotrypsin-like enzyme with strong preference for tyrosine over phenylalanine at the P1 cleavage position...
May 30, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28555004/epigenetic-signature-a-new-player-as-predictor-of-clinically-significant-prostate-cancer-pca-in-patients-on-active-surveillance-as
#15
REVIEW
Matteo Ferro, Paola Ungaro, Amelia Cimmino, Giuseppe Lucarelli, Gian Maria Busetto, Francesco Cantiello, Rocco Damiano, Daniela Terracciano
Widespread prostate-specific antigen (PSA) testing notably increased the number of prostate cancer (PCa) diagnoses. However, about 30% of these patients have low-risk tumors that are not lethal and remain asymptomatic during their lifetime. Overtreatment of such patients may reduce quality of life and increase healthcare costs. Active surveillance (AS) has become an accepted alternative to immediate treatment in selected men with low-risk PCa. Despite much progress in recent years toward identifying the best candidates for AS in recent years, the greatest risk remains the possibility of misclassification of the cancer or missing a high-risk cancer...
May 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28554670/serine-protease-isoforms-in-gloydius-intermedius-venom-full-sequences-molecular-phylogeny-and-evolutionary-implications
#16
Zhang-Min Yang, Hui Yu, Zhen-Zhen Liu, Jian-Zhu Pei, Yu-E Yang, Su-Xian Yan, Cui Zhang, Wen-Long Zhao, Zhe-Zhi Wang, Ying-Ming Wang, Inn-Ho Tsai
Nine distinct venom serine proteases (vSPs) of Gloydius intermedius were studied by transcriptomic, sub-proteomic and phylogenetic analyses. Their complete amino acid sequences were deduced after Expression Sequence Tag (EST) analyses followed by cDNA cloning and sequencing. These vSPs appear to be paralogs and contain the catalytic triads and 1-4 potential N-glycosylation sites. Their relative expression levels evaluated by qPCR were grossly consistent with their EST hit-numbers. The major vSPs were purified by HPLC and their N-terminal sequences matched well to the deduced sequences, while fragments of the minor vSPs were detected by LC-MS/MS identification...
May 26, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28552561/fxii-promotes-proteolytic-processing-of-the-lrp1-ectodomain
#17
Lukasz Wujak, Christina Hesse, Katherina Sewald, Danny Jonigk, Peter Braubach, Gregor Warnecke, Hans-Gerd Fieguth, Armin Braun, Günter Lochnit, Philipp Markart, Liliana Schaefer, Malgorzata Wygrecka
BACKGROUND: Factor XII (FXII) is a serine protease that is involved in activation of the intrinsic blood coagulation, the kallikrein-kinin system and the complement cascade. Although the binding of FXII to the cell surface has been demonstrated, the consequence of this event for proteolytic processing of membrane-anchored proteins has never been described. METHODS: The effect of FXII on the proteolytic processing of the low-density lipoprotein receptor-related protein 1 (LRP1) ectodomain was tested in human primary lung fibroblasts (hLF), alveolar macrophages (hAM) and in human precision cut lung slices (hPCLS)...
August 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28549900/four-decades-of-ocular-renin-angiotensin-and-kallikrein-kinin-systems-1977-2017
#18
REVIEW
Rajko Igić
This review offers a contemporary history of the renin-angiotensin (RAS) and kallikrein-kinin (KKS) systems with emphasis on how these complex systems affect the eye. It describes the types of communication (cross-talk) between the two systems and evaluates their potential role in the development of diabetic retinopathy, diabetic macular edema, age-related macular degeneration, glaucoma, and uveitis. In addition to detailing the important physiological actions of components of the RAS and KKS, possibilities are suggested for new therapeutic avenues in the treatment of common ocular diseases...
May 23, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28543088/3d-quantitative-structure-activity-relationship-and-docking-studies-of-coumarin-derivatives-as-tissue-kallikrein-7-inhibitors
#19
Xin Zheng, Mengxi He, Xiao Tan, Jun Zheng, Fangyu Wang, Sen Liu
OBJECTIVES: Kallikrein 7 (KLK7) is a secreted serine protease that plays important roles in skin desquamation and tumour progression, which makes it an attracting drug target. To guide the design of KLK7 inhibitors, a series of coumarin-based inhibitors were used to perform 3D-quantitative structure-activity relationship analysis. METHODS: 3D conformations of 37 inhibitors were generated and used to construct CoMFA and CoMSIA models. Then a complex model between the inhibitors and KLK7 was built with molecular docking...
May 23, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28542440/plasma-kallistatin-in-critically-ill-patients-with-severe-sepsis-and-septic-shock
#20
Wei-Chieh Lin, Chang-Wen Chen, Lee Chao, Julie Chao, Yee-Shin Lin
Kallistatin, an endogenous serine proteinase inhibitor, is protective against sepsis in animal models. The aim of this study was to determine the plasma concentration of kallistatin in intensive care unit (ICU) patients with severe sepsis and septic shock and to determine their potential correlation with disease severity and outcomes. We enrolled 86 ICU patients with severe sepsis and septic shock. Their plasma concentrations of kallistatin, kallikrein, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8 were measured by enzyme-linked immunosorbent assay...
2017: PloS One
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