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Kallikrein

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https://www.readbyqxmd.com/read/28726131/detection-of-enzyme-activity-and-inhibition-during-studies-in-solution-in-vitro-and-in-vivo-with-catalycest-mri
#1
Sanhita Sinharay, Edward A Randtke, Christine M Howison, Natalia A Ignatenko, Mark D Pagel
PURPOSE: The detection of enzyme activities and evaluation of enzyme inhibitors have been challenging with magnetic resonance imaging (MRI). To address this need, we have developed a diamagnetic, nonmetallic contrast agent and a protocol known as catalyCEST MRI that uses chemical exchange saturation transfer (CEST) to detect enzyme activity as well as enzyme inhibition. PROCEDURES: We synthesized a diamagnetic MRI contrast agent that has enzyme responsive and enzyme unresponsive CEST signals...
July 19, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28722103/decreased-levels-of-active-upa-and-klk8-assessed-by-111-in-mica-401-binding-correlate-with-the-seizure-burden-in-an-animal-model-of-temporal-lobe-epilepsy
#2
Stephan Missault, Lore Peeters, Halima Amhaoul, David Thomae, Annemie Van Eetveldt, Barbara Favier, Anagha Thakur, Jeroen Van Soom, Asla Pitkänen, Koen Augustyns, Jurgen Joossens, Steven Staelens, Stefanie Dedeurwaerdere
OBJECTIVE: Urokinase-type plasminogen activator (uPA) and kallikrein-related peptidase 8 (KLK8) are serine proteases that contribute to extracellular matrix (ECM) remodeling after brain injury. They can be labelled with the novel radiotracer [(111) In]MICA-401. As the first step in exploring the applicability of [(111) In]MICA-401 in tracing the mechanisms of postinjury ECM reorganization in vivo, we performed in vitro and ex vivo studies, assessing [(111) In]MICA-401 distribution in the brain in two animal models: kainic acid-induced status epilepticus (KASE) and controlled cortical impact (CCI)-induced traumatic brain injury (TBI)...
July 19, 2017: Epilepsia
https://www.readbyqxmd.com/read/28720353/kallikreins-panel-for-prostate-cancer-aggressiveness-prediction-more-is-not-enough
#3
EDITORIAL
Guillaume Ploussard
No abstract text is available yet for this article.
February 2017: European Urology Focus
https://www.readbyqxmd.com/read/28712126/evidence-of-an-abnormal-epithelial-barrier-in-active-untreated-and-corticosteroid-treated-eosinophilic-esophagitis
#4
Dagmar Simon, Basile Page, Monique Vogel, Christian Bussmann, Carine Blanchard, Alex Straumann, Hans-Uwe Simon
BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic, immune/antigen-mediated disease characterized by symptoms related to esophageal dysfunction and an eosinophil-predominant inflammation. This study has aimed to investigate whether the recently observed sensitization to Candida albicans in EoE patients is owing to pre-existing disease and its underlying abnormal epithelial barrier or, alternatively, is linked to corticosteroid (CS) therapy. METHODS: Medical histories, as well as serum and tissue samples of 60 EoE patients (15 CS-naive, 45 with current or previous CS therapy) and 20 controls, stored in the Swiss Eosinophilic Esophagitis Database (SEED) and Biobank, were analyzed...
July 16, 2017: Allergy
https://www.readbyqxmd.com/read/28699813/prolylcarboxypeptidase-prcp-inhibitors-and-the-therapeutic-uses-thereof-a-patent-review
#5
Thomas H Graham
Prolylcarboxypeptidase (PrCP) is a serine protease that produces or degrades signaling proteins in several important pathways including the renin-angiotensin system (RAS), kallikrein-kinin system (KKS) and pro-opiomelanocortin (POMC) system. PrCP has the potential to be a therapeutic target for cardiovascular, inflammatory and metabolic diseases. Numerous classes of PrCP inhibitors have been developed by rational drug design and from high-throughput screening hits. These inhibitors have been tested in mouse models to assess their potential as new therapeutics...
July 12, 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/28690145/salivary-gland-transcripts-of-the-kissing-bug-panstrongylus-chinai-a-vector-of-chagas-disease
#6
Hirotomo Kato, Ryan C Jochim, Eduardo A Gomez, Shunsuke Tsunekawa, Jesus G Valenzuela, Yoshihisa Hashiguchi
The saliva of hematophagous arthropods injected during blood feeding contains potent pharmacologically active components to counteract the host hemostatic and inflammatory systems. In the present study, dominant salivary gland transcripts of Panstrongylus chinai, a vector of Chagas disease, were analyzed by sequencing randomly selected clones of the salivary gland cDNA library. This analysis showed that 56.5% of the isolated transcripts coded for putative secreted proteins, of which 73.7% coded for proteins belonging to the lipocalin family...
July 6, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28687106/pathogenesis-of-hereditary-angioedema-the-role-of-the-bradykinin-forming-cascade
#7
REVIEW
Allen P Kaplan, Kusumam Joseph
Hereditary angioedema (HAE) is an autosomal-dominant disorder owing to mutations in the C1 inhibitor gene. Type I is characterized by a low C1 inhibitor protein level and diminished functional activity, whereas type II has a normal (or elevated) protein level but diminished function. When functional levels drop beyond 40% of normal, attacks of swelling are likely to occur due to overproduction of bradykinin. Angioedema can be peripheral, abdominal, or laryngeal. The typical duration of episodes is 3 days. Therapies include C1 inhibitor replacement for prophylaxis or acute therapy, whereas inhibition of kallikrein or blockade at the bradykinin receptor level can interrupt acute episodes of swelling...
August 2017: Immunology and Allergy Clinics of North America
https://www.readbyqxmd.com/read/28685545/decreased-plasma-kallikrein-5-concentrations-in-patients-with-chronic-spontaneous-urticaria
#8
A Grzanka, A Damasiewicz-Bodzek, M Szumska, A Kasperska-Zajac
Little is known about the role of the kallikrein-kinin system in chronic spontaneous urticaria (CSU). Kallikrein 5 (KLK5), a trypsin-like enzyme, is the most abundant in the skin and plays a role in itching and inflammatory reaction. In this study, we determined plasma KLK5 concentration, and its associations with acute phase response in CSU patients. Concentrations of KLK5 in plasma and CRP in serum were measured in patients with CSU of varying severity and in the healthy subjects. Plasma KLK5 concentrations were significantly lower in CSU (all) and moderate-severe CSU patients, as compared with the controls...
April 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28672746/study-of-kallikrein-related-peptidase-6-klk6-and-its-complex-with-%C3%AE-1-antitrypsin-in-biological-fluids
#9
Dimitrios Korbakis, Antoninus Soosaipillai, Eleftherios P Diamandis
BACKGROUND: Human kallikrein-related peptidase 6 (KLK6) is a member of the kallikrein family of serine proteases. KLK6 is synthesized as a preproenzyme, mainly in tissues of the central nervous system (CNS), and secreted as an inactive precursor. Serum KLK6 is a biomarker of unfavorable prognosis for ovarian cancer, but its sensitivity for early detection is relatively low. Differential glycosylation of KLK6 has been identified in ascites fluid obtained from ovarian cancer patients, suggesting the presence of unique KLK6 isoforms in biological samples...
June 24, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28668641/glycosylation-of-human-vaspin-serpina12-and-its-impact-on-serpin-activity-heparin-binding-and-thermal-stability
#10
Kathrin Oertwig, David Ulbricht, Stefanie Hanke, Jan Pippel, Kathrin Bellmann-Sickert, Norbert Sträter, John T Heiker
Vaspin is a glycoprotein with three predicted glycosylation sites at asparagine residues located in proximity to the reactive center loop and close to domains that play important roles in conformational changes underlying serpin function. In this study, we have investigated the glycosylation of human vaspin and its effects on biochemical properties relevant to vaspin function. We show that vaspin is modified at all three sites and biochemical data demonstrate that glycosylation does not hinder inhibition of the target protease kallikrein 7...
June 29, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28655904/danhong-injection-reduces-vascular-remodeling-and-up-regulates-the-kallikrein-kinin-system-in-spontaneously-hypertensive-rats
#11
Xiaohu Yang, John Orgah, Dandan Wang, Guanwei Fan, Hu Jingyang, Jihong Han, Gangjian Qin, Xiumei Gao, Yan Zhu
Although Danhong injection (DHI) is one of the most prescribed cardiovascular medicines in China, its therapeutic indications and mechanisms remain partially defined. We now identify molecular targets of DHI in resistance vasculatures and demonstrate its role in vascular function and blood pressure (BP) regulation. BP was determined in DHI, Losartan, and placebo- treated Spontaneously Hypertensive Rats (SHR) by both noninvasive and invasive measurements. Vasorelaxation was examined both in conduit and resistance vasculature by ex vivo aortic rings...
June 27, 2017: Scientific Reports
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
#12
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
#13
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
#14
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
#15
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...
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
#16
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
#17
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
#18
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
#19
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
#20
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
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