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Kallikrein

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https://www.readbyqxmd.com/read/28824923/activation-of-inflammatory-and-pro-thrombotic-pathways-in-acute-stress-cardiomyopathy
#1
Timothy P Fitzgibbons, Yvonne J K Edwards, Peter Shaw, Aline Iskandar, Mohamed Ahmed, Josiah Bote, Tejen Shah, Sumita Sinha, Robert E Gerszten, John F Keaney, Michael R Zile, Gerard P Aurigemma
Stress cardiomyopathy (SCM) is a unique cardiac disorder that more often occurs in women. SCM presents in a similar fashion as acute myocardial infarction (AMI), with chest pain, ECG changes, and congestive heart failure. The primary distinguishing feature is the absence of thrombotic coronary occlusion in SCM. How this reduction in cardiac function occurs in the absence of coronary occlusion remains unknown. Therefore, we tested the hypothesis that a targeted proteomic comparison of patients with acute SCM and AMI might identify relevant mechanistic differences...
2017: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28824910/the-effects-of-the-contact-activation-system-on-hemorrhage
#2
REVIEW
Fabrício Simão, Edward P Feener
The contact activation system (CAS) exerts effects on coagulation via multiple mechanisms, which modulate both the intrinsic and extrinsic coagulation cascades as well as fibrinolysis and platelet activation. While the effects of the CAS on blood coagulation measured as activated partial thromboplastin time shortening are well documented, genetic mutations that result in deficiencies in the expression of either plasma prekallikrein (PPK) or factor XII (FXII) are not associated with spontaneous bleeding or increased bleeding risk during surgery...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28824610/mast-cell-coupling-to-the-kallikrein-kinin-system-fuels-intracardiac-parasitism-and-worsens-heart-pathology-in-experimental-chagas-disease
#3
Clarissa R Nascimento, Daniele Andrade, Carla Eponina Carvalho-Pinto, Rafaela Rangel Serra, Lucas Vellasco, Guilherme Brasil, Erivan Schnaider Ramos-Junior, Julia Barbalho da Mota, Larissa Nogueira Almeida, Marcus V Andrade, Maria de Nazaré Correia Soeiro, Luiz Juliano, Patrícia Hessab Alvarenga, Ana Carolina Oliveira, Fernando Lencastre Sicuro, Antônio C Campos de Carvalho, Erik Svensjö, Julio Scharfstein
During the course of Chagas disease, infectious forms of Trypanosoma cruzi are occasionally liberated from parasitized heart cells. Studies performed with tissue culture trypomastigotes (TCTs, Dm28c strain) demonstrated that these parasites evoke neutrophil/CXCR2-dependent microvascular leakage by activating innate sentinel cells via toll-like receptor 2 (TLR2). Upon plasma extravasation, proteolytically derived kinins and C5a stimulate immunoprotective Th1 responses via cross-talk between bradykinin B2 receptors (B2Rs) and C5aR...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28823846/itraq-based-investigation-of-plasma-proteins-in-hiv-infected-and-hiv-hbv-coinfected-patients-c9-and-klk-are-related-to-hiv-hbv-coinfection
#4
Tao Sun, Li Liu, Ao Wu, Yujiao Zhang, Xiaofang Jia, Lin Yin, Hongzhou Lu, Lijun Zhang
OBJECTIVES: Human immunodeficiency virus (HIV) and hepatitis B virus (HBV) share similar routes of transmission, and rapid progression of hepatic and immunodeficiency diseases has been observed in coinfected individuals. Our main objective was to investigate the molecular mechanism of HIV/HBV coinfections. METHODS: We selected HIV infected and HIV/HBV coinfected patients with and without Highly Active Antiretroviral Therapy (HAART). Low abundance proteins enriched using a multiple affinity removal system (MARS) were labeled with isobaric tags for relative and absolute quantitation (iTRAQ) kits and analyzed using liquid chromatography-mass spectrometry (LC-MS)...
August 16, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28820397/long-term-feeding-with-bioactive-tripeptides-in-aged-hypertensive-and-normotensive-rats-special-focus-on-blood-pressure-and-bradykinin-induced-vascular-reactivity
#5
A Siltari, J Roivanen, R Korpela, H Vapaatalo
Bradykinin is the main player of the kallikrein-kinin system. Bradykinin-induced vasodilatation is age-dependent; this is believed to be associated with the level of expression of the two bradykinin receptors (BR1 and BR2) in the vasculature. The aim of this study was to clarify bradykinin-induced vascular reactivity of spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto rats (WKY) after 6 weeks' consumption of a drink containing bioactive tripeptides (Ile-Pro-Pro, Val-Pro-Pro and Leu-Pro-Pro)...
June 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28817220/klk14-interactions-with-hai-1-and-hai-2-serine-protease-inhibitors-a-molecular-dynamics-and-relative-free-energy-calculations-study
#6
Christian Solís-Calero, Hernandes F Carvalho
Kallikrein 14 (KLK14) is a serine protease linked to several pathologies including prostate cancer and positively correlates with Gleason score. Though KLK14 functioning in cancer is poorly understood, it has been implicated in HGF/Met signaling, given that KLK14 proteolytically inhibits HGF activator-inhibitor 1 (HAI-1), which strongly inhibits pro-HGF activators, thereby contributing to tumor progression. In this work, KLK14 binding to either hepatocyte growth factor activator inhibitor type-1 (HAI-1) or type-2 (HAI-2) was essayed using homology modeling, molecular dynamic simulations and free-energy calculations through MM/PBSA and MM/GBSA...
August 17, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28816340/coagulation-factor-xii-regulates-inflammatory-responses-in-human-lungs
#7
Rosanna Hess, Lukasz Wujak, Christina Hesse, Katherina Sewald, Danny Jonigk, Gregor Warnecke, Hans-Gerd Fieguth, Steven de Maat, Coen Maas, Francesco Bonella, Klaus T Preissner, Benjamin Weiss, Liliana Schaefer, Wolfgang M Kuebler, Philipp Markart, Malgorzata Wygrecka
Increased procoagulant activity in the alveolar compartment and uncontrolled inflammation are hallmarks of the acute respiratory distress syndrome (ARDS). Here, we investigated whether the contact phase system of coagulation is activated and may regulate inflammatory responses in human lungs. Components of the contact phase system were characterized in bronchoalveolar lavage fluids (BALF) from 54 ARDS patients and 43 controls, and their impact on cytokine/chemokine expression in human precision cut lung slices (PCLS) was assessed by a PCR array...
August 17, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28810574/tissue-kallikrein-protects-against-ischemic-stroke-by-suppressing-tlr4-nf-%C3%AE%C2%BAb-and-activating-nrf2-signaling-pathway-in-rats
#8
Jiawei Yang, Jianhua Su, Fen Wan, Nan Yang, Haibo Jiang, Mingming Fang, Hang Xiao, Jun Wang, Jinrong Tang
Brain damage following cerebral ischemia-reperfusion (I/R) is a complicated pathophysiological course, in which inflammation and oxidative stress have been suggested to serve an important role. Toll-like receptor 4 (TLR4) has been suggested to be involved in secondary inflammatory process in cerebral ischemia. Nuclear factor erythroid 2-related factor 2 (Nrf2), an important regulator of the antioxidant host defense, maintains the cellular redox homeostasis. Tissue kallikrein (TK) has been proven to elicit a variety of biological effects in ischemic stroke through its anti-inflammatory and anti-oxidant properties...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28808141/a-critical-role-for-plasma-kallikrein-in-the-pathogenesis-of-autoantibody-induced-arthritis
#9
Aizhen Yang, Junsong Zhou, Bo Wang, Jihong Dai, Robert W Colman, Wenchao Song, Yi Wu
The plasma kallikrein-kinin system (KKS) consists of serine proteases, prekallikrein (pKal) and factor XII (FXII), and a cofactor, high-MW kininogen (HK). Upon activation, activated pKal and FXII cleave HK to release bradykinin. Activation of this system has been noted in patients with rheumatoid arthritis, and its pathogenic role has been characterized in animal arthritic models. In this study, we generated 2 knockout mouse strains that lacked pKal and HK and determined the role of KKS in autoantibody-induced arthritis...
August 14, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28783084/enter-the-dragon-the-dynamic-and-multifunctional-evolution-of-anguimorpha-lizard-venoms
#10
Ivan Koludarov, Timothy Nw Jackson, Bianca Op den Brouw, James Dobson, Daniel Dashevsky, Kevin Arbuckle, Christofer J Clemente, Edward J Stockdale, Chip Cochran, Jordan Debono, Carson Stephens, Nadya Panagides, Bin Li, Mary-Louise Roy Manchadi, Aude Violette, Rudy Fourmy, Iwan Hendrikx, Amanda Nouwens, Judith Clements, Paolo Martelli, Hang Fai Kwok, Bryan G Fry
While snake venoms have been the subject of intense study, comparatively little work has been done on lizard venoms. In this study, we have examined the structural and functional diversification of anguimorph lizard venoms and associated toxins, and related these results to dentition and predatory ecology. Venom composition was shown to be highly variable across the 20 species of Heloderma, Lanthanotus, and Varanus included in our study. While kallikrein enzymes were ubiquitous, they were also a particularly multifunctional toxin type, with differential activities on enzyme substrates and also ability to degrade alpha or beta chains of fibrinogen that reflects structural variability...
August 6, 2017: Toxins
https://www.readbyqxmd.com/read/28780894/gene-therapy-for-hypertension
#11
Ludovit Paulis, Heinrich Franke, Fedor Simko
The control of hypertension and the resulting cardiovascular events is still insufficient. Thus, the search for novel means for blood pressure (BP) reduction remains worth further clinical and research attention. The advances in vector and construct design sketch the use of gene therapy in hypertension. Areas covered: The authors have searched for studies using gene therapy in hypertension reporting BP outcomes. They have identified 63 experimental studies demonstrating feasible targeting of the classical and new renin-angiotensin-aldosterone system, β1-adrenergic receptor, NO-cGMP axis, endothelin, natriuretic peptides, kallikrein system, cytochrome P-450 hydroxylase, oncogenes, growth factors, interleukins, angiopoietin-1, adrenomedullin or Klotho in small rodents...
August 7, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28772209/renin-angiotensin-aldosterone-raas-the-ubiquitous-system-for-homeostasis-and-pathologies
#12
Seema Patel, Abdur Rauf, Haroon Khan, Tareq Abu-Izneid
Renin-angiotensin-aldosterone system (RAAS) is a vital system of human body, as it maintains plasma sodium concentration, arterial blood pressure and extracellular volume. Kidney-secreted renin enzyme acts on its substrate to form angiotensin II, a versatile effector peptide hormone. Every organ is affected by RAAS activation and the resultant hypertension, cell proliferation, inflammation, and fibrosis. The imbalance of renin and angiotensin II can result in an overwhelming number of chronic and acute diseases...
July 31, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28762124/a-randomized-trial-of-early-detection-of-clinically-significant-prostate-cancer-proscreen-study-design-and-rationale
#13
Anssi Auvinen, Antti Rannikko, Kimmo Taari, Paula Kujala, Tuomas Mirtti, Anu Kenttämies, Irina Rinta-Kiikka, Terho Lehtimäki, Niku Oksala, Kim Pettersson, Teuvo L Tammela
The current evidence of PSA-based prostate cancer screening shows a reduction in cause-specific mortality, but with substantial overdiagnosis. Recently, new developments in detection of clinically relevant prostate cancer include multiple kallikreins as biomarkers besides PSA, and multiparametric magnetic resonance imaging (mpMRI) for biopsy decision. They offer opportunities for improving the outcomes in screening, particularly reduction in overdiagnosis and higher specificity for potentially lethal cancer...
July 31, 2017: European Journal of Epidemiology
https://www.readbyqxmd.com/read/28761938/down-regulation-of-hk7-in-the-sera-of-breast-cancer-and-benign-breast-disease-patients
#14
Samina Ejaz, Faiz-Ul-Hassan Nasim, Muhammad Ashraf, Gulzar Ahmad
INTRODUCTION: Breast cancer is known as a leading cause of cancer-related death among women all over the world. Biomarkers facilitate diagnosis at the earliest possible stage and better prognosis of the disease. Hence, may help to improve the overall survival rate among breast cancer patients. To find a better diagnostic/prognostic marker we evaluated human tissue kallikrein 7 (hK7) as biomarker of breast cancer. hK7 is a secreted serine protease having chymotrypsin like activity. Serum hK7 is known to have aberrant expression in ovarian and prostate cancer but has not been yet studied in breast cancer...
July 2017: Heliyon
https://www.readbyqxmd.com/read/28755528/tissue-kallikrein-related-peptidase-4-klk4-a-novel-biomarker-in-triple-negative-breast-cancer
#15
Feng Yang, Michaela Aubele, Axel Walch, Eva Gross, Rudolf Napieralski, Shuo Zhao, Nancy Ahmed, Marion Kiechle, Ute Reuning, Julia Dorn, Fred Sweep, Viktor Magdolen, Manfred Schmitt
Triple-negative breast cancer (TNBC), lacking the steroid hormone receptors ER and PR and the oncoprotein HER2, is characterized by its aggressive pattern and insensitivity to endocrine and HER2-directed therapy. Human kallikrein-related peptidases KLK1-15 provide a rich source of serine protease-type biomarkers associated with tumor growth and cancer progression for a variety of malignant diseases. In this study, recombinant KLK4 protein was generated and affinity-purified KLK4-directed polyclonal antibody pAb587 established to allow localization of KLK4 protein expression in tumor cell lines and archived formalin-fixed, paraffin-embedded TNBC tumor tissue specimens...
July 28, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28754951/mass-spectrometry-based-determination-of-kallikrein-related-peptidase-7-klk7-cleavage-preferences-and-subsite-dependency
#16
Lakmali Munasinghage Silva, Thomas Stoll, Thomas Kryza, Carson Ryan Stephens, Marcus Lachlan Hastie, Helen Frances Irving-Rodgers, Ying Dong, Jeffrey John Gorman, Judith Ann Clements
The cleavage preferences of Kallikrein-related peptidase 7 (KLK7) have previously been delineated using synthetic peptide libraries of fixed length, or single protein chains and have suggested that KLK7 exerts a chymotryptic-like cleavage preference. Due to the short length of the peptides utilised, only a limited number of subsites have however been assessed. To determine the subsite preferences of KLK7 in a global setting, we used a mass spectrometry (MS)-based in-depth proteomics approach that utilises human proteome-derived peptide libraries of varying length, termed Proteomic Identification of protease Cleavage Sites (PICS)...
July 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28745506/structure-dependent-hematological-effects-of-per-and-polyfluoroalkyl-substances-on-activation-of-plasma-kallikrein-kinin-system-cascade
#17
Qian S Liu, Yuzhen Sun, Guangbo Qu, Yanmin Long, Xingchen Zhao, Aiqian Zhang, Qunfang Zhou, Ligang Hu, Guibin Jiang
Per- and polyfluoroalkyl substances (PFASs) are a global concern because of their ubiquitous occurrence and high persistence in human blood, and increasing amounts of unidentified fluorinated compounds are now becoming new exposure issues. This study aims to investigate the structure-related effects of PFASs on the activation of the plasma kallikrein-kinin system (KKS). The effects of 20 PFASs and the related long-chain aliphatic compounds were screened, and their binding affinities for the initial zymogen, Hagmen factor XII (FXII) in the KKS, were evaluated by molecular docking analysis...
August 15, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28744223/modulation-of-the-plasma-kallikrein-kinin-system-proteins-performed-by-heparan-sulfate-proteoglycans
#18
REVIEW
Guacyara Motta, Ivarne L S Tersariol
Human plasma kallikrein-kinin system proteins are related to inflammation through bradykinin. In the proximity of its target cells, high molecular weight kininogen (H-kininogen) is the substrate of plasma kallikrein, which releases bradykinin from H-kininogen. Heparan sulfate proteoglycans (HSPGs) play a critical role in either recruiting kinin precursors from the plasma, or in the assembly of kallikrein-kinin system components on the cell surface. Furthermore, HSPGs mediate the endocytosis and activation of H-kininogen and plasma prekallikrein...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28743596/the-plasma-contact-system-a-protease-cascade-at-the-nexus-of-inflammation-coagulation-and-immunity
#19
REVIEW
Henri Weidmann, Laura Heikaus, Andy T Long, Clément Naudin, Hartmut Schlüter, Thomas Renné
The contact system is a potent procoagulant and proinflammatory plasma protease cascade that is initiated by binding ("contact")-induced, auto-activation of factor XII zymogen. Formed active serine protease FXIIa then cleaves plasma prekallikrein to kallikrein that in turn liberates the mediator bradykinin from its precursor high molecular weight kininogen. Bradykinin induces inflammation with implications for host defense and innate immunity. FXIIa also triggers the intrinsic pathway of coagulation that has been shown to critically contribute to thrombosis...
July 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28743213/kallikrein-related-peptidase-4-contributes-to-the-tumor-metastasis-of-oral-squamous-cell-carcinoma
#20
Zhi Cui, Ye Cui, Gan Luo, Shuting Yang, Xinlian Ling, Yixin Lou, Xinhua Sun
Oral squamous cell carcinoma (OSCC) is a disfiguring malignancy and significantly impacts the quality of patient's life. Kallikrein-related peptidase 4 (KLK4), which is closely related to cancers, is highly expressed in OSCC. To explore the biological function of KLK4 in OSCC, a KLK4-specific shRNA was used to silence its endogenous expression, and then the migration and invasion of OSCC cells were explored. Results of our study showed that silencing KLK4 inhibited the migration and invasion of OSCC cells. The protein levels of epithelial mesenchymal transition-associated markers and proteases were also altered by KLK4 silencing...
September 2017: Bioscience, Biotechnology, and Biochemistry
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