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Regulation of intestinal permeability: The role of proteases

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World Journal of Gastroenterology 2017年第12期23卷 2106-2123页

作者： Hanne Van Spaendonk Hannah Ceuleers Leonie Witters Eveline Patteet Jurgen Joossens Koen Augustyns Anne-Marie Lambeir Ingrid De Meester Joris G De Man Benedicte Y De Winter Laboratory of Experimental Medicine and Pediatrics Division of GastroenterologyUniversity of Antwerp Laboratory of Medicinal Chemistry and Antwerp Drug Discovery Network University of Antwerp Laboratory of Medical Biochemistry University of Antwerp

The gastrointestinal barrier is-with approximately 400 m^2-the human body's largest surface separating the external environment from the internal milieu. This barrier serves a dual function: permitting the absorption of nutrients, water and electrolytes on the one hand, while limiting host contact with noxious luminal antigens on the other hand. To maintain this selective barrier, junction protein complexes seal the intercellular space between adjacent epithelial cells and regulate the paracellular transport. Increased intestinal permeability is associated with and suggested as a player in the pathophysiology of various gastrointestinal and extraintestinal diseases such as inflammatory bowel disease, celiac disease and type 1 diabetes. The gastrointestinal tract is exposed to high levels of endogenous and exogenous proteases, both in the lumen and in the mucosa. There is increasing evidence to suggest that a dysregulation of the protease/antiprotease balance in the gut contributes to epithelial damage and increased permeability. Excessive proteolysis leads to direct cleavage of intercellular junction proteins, or to opening of the junction proteins via activation of protease activated receptors. In addition, proteases regulate the activity and availability of cytokines and growth factors, which are also known modulators of intestinal permeability. This review aims at outlining the mechanisms by which proteases alter the intestinal permeability. More knowledge on the role of proteases in mucosal homeostasis and gastrointestinal barrier function will definitely contribute to the identification of new therapeutic targets for permeability-related diseases.

关键词： Intestinal permeability Intestinal barrier Tight junction Paracellular permeability proteases Proteinase-activated receptor Protease inhibitor Antiproteases

Correction to:proteases from the marine bacteria in the genus Pseudoalteromonas:diversity,characteristics,ecological roles,and application potentials

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Marine Life Science & Technology 2020年第4期2卷 456-457页

作者： Xiu-Lan Chen Yan Wang Peng Wang Yu-Zhong Zhang State Key Laboratory of Microbial Technology Shandong UniversityQingdao 266237China College of Marine Life Sciences Institute for Advanced Ocean StudyOcean University of ChinaQingdao 266003China Laboratory for Marine Biology and Biotechnology Pilot National Laboratory for Marine Science and Technology(Qingdao)Qingdao 266373China

The original article can be found online.

关键词： proteases Pseudoalteromonas Diversity Characteristics Ecological roles Application potentials COLLAGENOLYTIC SERINE-PROTEASE SP-NOV. DEEP-SEA SP. NOV. EMENDED DESCRIPTION ORGANIC NITROGEN DESEASIN MCP-01 COMB. NOV SP SM9913 EXTRACELLULAR proteases

Molecular docking of cyanine and squarylium dyes with SARS-CoV-2 proteases NSP3, NSP5 and NSP12

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Quantitative Biology 2021年第4期9卷 440-450页

作者： Pavel Pronkin Alexander Tatikolov n.m.emanuel institute of biochemical physics russian academy of sciencesmoscow 119991russia

Background:The outbreak and continued spread of coronavirus infection(COVID-19)sets the goal of finding new tools and methods to develop analytical procedures and tests to detect,study infection and prevent morbidity.Methods:The noncovalent binding of cyanine and squarylium dyes of different classes(60 compounds in total)with the proteases NSP3,NSP5,and NSP12 of SARS-CoV-2 was studied by the method of molecular docking.Results:The interaction energies and spatial configurations of dye molecules in complexes with NSP3,NSP5,and NSP12 have been determined.Conclusion:A number of anionic dyes showing lower values of the total energy Etot could be recommended for practical research in the development of agents for the detection and inactivation of the coronavirus.

关键词： SARS-CoV-2 proteases polymethine dyes squarylium dyes noncovalent interaction molecular docking

Preparation and characterization of asymmetric ultrafiltration membrane for effective recovery of proteases from surimi wash water

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Frontiers of Chemical Science and Engineering 2012年第2期6卷 184-191页

作者： Nora'aini ALI Fadhilati HASSAN Sofiah HAMZAH Department of Engineering Science Faculty of Science and Technology University Malaysia Terengganu 21030 Kuala Terengganu Malaysia

The wash water generated from the surimi processing industry contains a large amount of proteases which are widely used in the food and biotechnology industries. Asymmetric polysulfone and polyethersulfone ultrafiltration （PSf-UF and PES-UF） membranes with three different polymer concentrations were screened for their abilities to recover proteases from surimi wash water. In- house fabricated membranes were prepared via a simple dry/wet phase inversion technique and were characterized in terms of permeability coefficient, membrane morphol- ogy and molecular weight cut-off （MWCO）. The ability of the UF membranes to remove commercial proteases was tested at various pressures （up to 10 bars）. The membrane with the best performance, 15 wt-% PSf-UF, was further tested with actual surimi wash water. The effect of the pH of the feed solution （4 to 8） in the pre-treatment stage was also evaluated to recover the highest amount of proteases. The highest retention of protease was 96% with a flux of 25.6 L/（mZ.h） which was achieved with the 15 wt-% PSf- UF membrane.

关键词： membrane ultrafiltration proteases surimi wash water

High-throughput screening of SARS-CoV-2 main and papain-like protease inhibitors

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Protein & Cell 2023年第1期14卷 17-27页

作者： Yi Zang Mingbo Su Qingxing Wang Xi Cheng Wenru Zhang Yao Zhao Tong Chen Yingyan Jiang Qiang Shen Juan Du Qiuxiang Tan Peipei Wang Lixin Gao Zhenming Jin Mengmeng Zhang Cong Li Ya Zhu Bo Feng Bixi Tang Han Xie Ming-Wei Wang Mingyue Zheng Xiaoyan Pan Haitao Yang Yechun Xu Beili Wu Leike Zhang Zihe Rao Xiuna Yang Hualiang Jiang Gengfu Xiao Qiang Zhao Jia Li The National Center for Drug Screening Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China State Key Laboratory of Drug Research and CAS Key Laboratory of Receptor Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China School of Pharmaceutical Science and Technology Hangzhou Institute for Advanced StudyUCASHangzhou 310024China School of Chinese Materia Medica Nanjing University of Chinese MedicineNanjing 210023China University of Chinese Academy of Sciences Beijing 100049China State Key Laboratory of Virology Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan 430071China Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China CAS Center for Excellence in Biomacromolecules Chinese Academy of SciencesBeijing 100101China Zhongshan Branch the Institute of Drug Discovery and DevelopmentChinese Academy of SciencesGuangdong 528400China

The global COVID-19 coronavirus pandemic has infected over 109 million people,leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment.Here,we screened about 1.8 million small molecules against the main protease(M^(pro))and papain like protease(PL^(pro)),two major proteases in severe acute respiratory syndrome-coronavirus 2 genome,and identified 1851M^(pro)inhibitors and 205 PL^(pro)inhibitors with low nmol/l activity of the best hits.Among these inhibitors,eight small molecules showed dual inhibition effects on both M^(pro)and PL^(pro),exhibiting potential as better candidates for COVID-19 treatment.The best inhibitors of each protease were tested in antiviral assay,with over 40%of M^(pro)inhibitors and over 20%of PL^(pro)inhibitors showing high potency in viral inhibition with low cytotoxicity.The X-ray crystal structure of SARS-CoV-2 M^(pro)in complex with its potent inhibitor 4a was determined at 1.8Åresolution.Together with docking assays,our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.

关键词： high-throughput screening SARS CoV-2 main papain-like proteases

Biofilm analyses and exoproduct release by clinical and environmental isolates of Burkholderia pseudomallei from Brazil

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Asian Pacific Journal of Tropical Medicine 2023年第7期16卷 321-328页

作者： Glaucia Morgana de Melo Guedes Crister JoséOcadaque Alyne Soares Freitas Rodrigo Machado Pinheiro Giovanna Barbosa Riello Silviane Praciano Bandeira Rossana de Aguiar Cordeiro Marcos Fábio Gadelha Rocha JoséJúlio Costa Sidrim Débora de Souza Collares Maia Castelo-Branco Department of Pathology and Legal Medicine Postgraduate Program in Medical MicrobiologyGroup of Applied Medical MicrobiologyFederal University of CearáFortalezaCEBrazil Department of Clinical and Toxicological Analysis School of PharmacyFederal University of CearáFortalezaCEBrazil Department of Pathology and Legal Medicine Postgraduate Program in Medical MicrobiologyLaboratory of Emerging and Reemerging PathogensFederal University of CearáFortalezaCEBrazil School of Veterinary Medicine Postgraduate Program in Veterinary SciencesState University of CearáFortalezaCEBrazil

Objective:To characterize biofilm production by clinical(n=21)and environmental(n=11)isolates of Burkholderia pseudomallei and evaluate the production of proteases,hemolysins and siderophores.Methods:Initially,the 32 strains were evaluated for biofilm production in Müller-Hinton broth-1%glucose(MH-1%glucose)and BHI broth-1%glucose,using the crystal violet staining technique.Subsequently,growing(48 h)and mature(72 h)biofilms were evaluated by confocal microscopy.Finally,the production of proteases,hemolysins and siderophores by planktonic aggregates,growing biofilms and mature biofilms was evaluated.Results:All isolates produced biofilms,but clinical isolates had significantly higher biomass in both MH-1%glucose(P<0.001)and BHI-glucose 1%(P=0.005).The structural analyses by confocal microscopy showed thick biofilms,composed of multiple layers of cells,homogeneously arranged,with mature biofilms of clinical isolates presenting higher biomass(P=0.019)and thickness of the entire area(P=0.029),and lower roughness coefficient(P=0.007)than those of environmental isolates.Protease production by growing biofilms was significantly greater than that of planktonic(P<0.001)and mature biofilms(P<0.001).Hemolysin release by planktonic aggregates was higher than that of biofilms(P<0.001).Regarding siderophores,mature biofilms presented higher production than growing biofilms(P<0.001)and planktonic aggregates(P<0.001).Conclusions:Clinical isolates have higher production of biofilms than their environmental counterparts;protease and siderophores seem important for growth and maintenance of Burkholderia pseudomallei biofilms.

关键词： Mangosteen Burkholderia pseudomallei Biofilms proteases Hemolysins Siderophores

Degradation of naturally occurring and engineered antimicrobial peptides by proteases

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Advances in Bioscience and Biotechnology 2011年第6期2卷 404-408页

作者： Bernard J. Moncla Kara Pryke Lisa Cencia Rohan Phillip W. Graebing Department of Obstetrics Gynecology and Reproductive Sciences University of Pittsburgh Pittsburgh USA.

We hypothesized that current antimicrobial peptides should be susceptible to proteolytic digestion. The antimicrobial peptides: Griffithinsin, RC-101, LL-37, LSA-5, PSC-RANTES and DJ007 were degraded by commercially available proteases. Two different species of anaerobic vaginal flora, Prevotella bivia and Porphyromonas asaccharolytica also degraded the materials. Griffithsin was resistant to digestion by 8 of the 9 proteases and the bacteria while LL-37 was the most sensitive to protease digestion. These data suggests most of the molecules may not survive for very long in the proteolytic rich environments in which they are intended to function.

关键词： Microbicides HIV Anti-HIV Antimicrobial Peptides proteases

Phytochemistry and pharmacological activities of Ficus carica latex: a systematic review

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Journal of Chinese Pharmaceutical Sciences 2022年第2期31卷 81-96页

作者： Haneen Mohammad Muhammed Alzweiri Department of Pharmaceutical Sciences School of PharmacyThe University of JordanAmmanJordan.Haneen

Ficus carica tree produces a white sap that is traditionally used for the treatment of skin conditions,such as warts.Ficus carica latex is considered a rich source of proteins and metabolites that have various pharmacological activities.Most of the latex pharmacological activities are attributed to its phenolic content,such as anticancer,antiviral,antioxidant,anti-angiogenic,hepatoprotective,and wound-healing activities.Moreover,Ficus carica latex contains proteases that are involved in the treatments of skin conditions,such as warts,and display antiparasitic activity.Additionally,chitinase enzymes and coumarins are isolated from Ficus carica latex and involved in the antimicrobial activities of latex.

关键词： Latex Ficus carica Moraceae proteases Ficin

Versatility of microbial proteases

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Advances in Enzyme Research 2013年第3期1卷 39-51页

作者： Veloorvalappil N. Jisha Robinson B. Smitha Selvanesan Pradeep Sasidharan Sreedevi Kizhakkepawothail N. Unni Sreedharan Sajith Prakasan Priji Moolakkariyil Sarath Josh Sailas Benjamin Enzyme Technology Laboratory Biotechnology Division Department of Botany University of Calicut Kerala India

proteases or peptidases constitute the largest group of enzymes in bio-industry with a long array of uses. They play an invincible role in industrial biotechnology, especially in detergent, food and pharmaceutical arena. This focused review encompasses an overview on alkaline proteases, mainly of microbial sources in a handy module. Following an introduction and general classification with evolutionary insight, major sources of proteases (animal, plant and microbial including fungal, bacterial), their general properties with mechanism of action and molecular masses are discussed. proteases fromBacillusspp. have been given special attention. In addition to this, an overview on the applications of proteases in detergent, tannery, food, metal recovery and waste treatment industries is also addressed briefly.

关键词： Review proteases Classification Sources Bacillus Industrial Uses