Cleavage of desmin by cysteine proteases: Calpains and cathepsin B

Meat Science ◽  
2004 ◽  
Vol 68 (3) ◽  
pp. 447-456 ◽  
Author(s):  
Caroline Pascale Baron ◽  
Susanne Jacobsen ◽  
Peter Patrick Purslow
Keyword(s):  
Cathepsin B ◽  
Cysteine Proteases

OnBlastocystissecreted cysteine proteases: a legumain-activated cathepsin B increases paracellular permeability of intestinal Caco-2 cell monolayers

Parasitology ◽  
2016 ◽  
Vol 143 (13) ◽  
pp. 1713-1722 ◽  
Author(s):  
C. NOURRISSON ◽  
I. WAWRZYNIAK ◽  
A. CIAN ◽  
V. LIVRELLI ◽  
E. VISCOGLIOSI ◽  
...  
Keyword(s):  
Cathepsin B ◽  
Proteolytic Enzymes ◽  
Cell Monolayer ◽  
Cysteine Proteases ◽  
Cell Permeability ◽  
Whole Genome Sequence ◽  
Intestinal Cell ◽  
Pathogenic Potential ◽  
Cell Monolayers ◽  
Culture Supernatants

SUMMARYBlastocystisspp. pathogenic potential remains unclear as these anaerobic parasitic protozoa are frequently isolated from stools of both symptomatic and asymptomatic subjects.In silicoanalysis of the whole genome sequence ofBlastocystissubtype 7 revealed the presence of numerous proteolytic enzymes including cysteine proteases predicted to be secreted. To assess the potential impact of proteases on intestinal cells and gut function, we focused our study on two cysteine proteases, a legumain and a cathepsin B, which were previously identified inBlastocystissubtype 7 culture supernatants. Both cysteine proteases were produced as active recombinant proteins. Activation of the recombinant legumain was shown to be autocatalytic and triggered by acidic pH, whereas proteolytic activity of the recombinant cathepsin B was only recorded after co-incubation with the legumain. We then measured the diffusion of 4-kDa FITC-labelled dextran across Caco-2 cell monolayers following exposition to eitherBlastocystisculture supernatants or each recombinant protease. BothBlastocystisculture supernatants and recombinant activated cathepsin B induced an increase of Caco-2 cell monolayer permeability, and this effect was significantly inhibited by E-64, a specific cysteine protease inhibitor. Our results suggest that cathepsin B might play a role in pathogenesis ofBlastocystisby increasing intestinal cell permeability.

scholarly journals Functional Analysis of Cathepsin B-like Cysteine Proteases fromLeishmania donovaniComplex

2002 ◽  
Vol 277 (28) ◽  
pp. 25305-25312 ◽  
Author(s):  
Ashwini Somanna ◽  
Vasanthakrishna Mundodi ◽  
Lashitew Gedamu
Keyword(s):  
Functional Analysis ◽  
Cathepsin B ◽  
Cysteine Proteases

scholarly journals Phylogenetic and Primary Sequence Characterization of Cathepsin B Cysteine Proteases from the Oxymonad FlagellateMonocercomonoides

2008 ◽  
Vol 55 (1) ◽  
pp. 9-17 ◽  
Author(s):  
JOEL B. DACKS ◽  
TEKLU KURU ◽  
NATALIA A. LIAPOUNOVA ◽  
LASHITEW GEDAMU
Keyword(s):  
Cathepsin B ◽  
Cysteine Proteases ◽  
Primary Sequence ◽  
Sequence Characterization

scholarly journals Giardia duodenalis Cathepsin B Proteases Degrade Intestinal Epithelial Interleukin-8 and Attenuate Interleukin-8-Induced Neutrophil Chemotaxis

2014 ◽  
Vol 82 (7) ◽  
pp. 2772-2787 ◽  
Author(s):  
James A. Cotton ◽  
Amol Bhargava ◽  
Jose G. Ferraz ◽  
Robin M. Yates ◽  
Paul L. Beck ◽  
...  
Keyword(s):  
Cathepsin B ◽  
Diarrheal Disease ◽  
Inflammatory Responses ◽  
Functional Gastrointestinal Disorders ◽  
Giardia Duodenalis ◽  
Cysteine Proteases ◽  
Interleukin 8 ◽  
Human Neutrophils ◽  
Intestinal Epithelial ◽  
Content Type

ABSTRACTGiardia duodenalis(syn.G. intestinalis,G. lamblia) infections are a leading cause of waterborne diarrheal disease that can also result in the development of postinfectious functional gastrointestinal disorders via mechanisms that remain unclear. Parasite numbers exceed 106trophozoites per centimeter of gut at the height of an infection. Yet the intestinal mucosa ofG. duodenalis-infected individuals is devoid of signs of overt inflammation.G. duodenalisinfections can also occur concurrently with infections with other proinflammatory gastrointestinal pathogens. Little is known of whether and how this parasite can attenuate host inflammatory responses induced by other proinflammatory stimuli, such as a gastrointestinal pathogen. Identifying hitherto-unrecognized parasitic immunomodulatory pathways, the present studies demonstrated thatG. duodenalistrophozoites attenuate secretion of the potent neutrophil chemoattractant interleukin-8 (CXCL8); these effects were observed in human small intestinal mucosal tissues and from intestinal epithelial monolayers, activated through administration of proinflammatory interleukin-1β orSalmonella entericaserovar Typhimurium. This attenuation is caused by the secretion ofG. duodenaliscathepsin B cysteine proteases that degrade CXCL8 posttranscriptionally. Furthermore, the degradation of CXCL8 viaG. duodenaliscathepsin B cysteine proteases attenuates CXCL8-induced chemotaxis of human neutrophils. Taken together, these data demonstrate for the first time thatG. duodenalistrophozoite cathepsins are capable of attenuating a component of their host's proinflammatory response induced by a separate proinflammatory stimulus.

Cloning and Expression of Fasciola gigantica Cathepsin-B Recombinant Proteins

2020 ◽  
Author(s):  
O. K. Raina ◽  
Andleeb Aftab ◽  
Savita Bisen ◽  
Rohit Lall ◽  
Shobha Yadav ◽  
...  
Keyword(s):  
Recombinant Proteins ◽  
Cathepsin B ◽  
Expression System ◽  
Cysteine Proteases ◽  
Scientific Data ◽  
Fasciola Gigantica ◽  
Cloning And Expression ◽  
Recombinant Antigens ◽  
Diagnostic Potential ◽  
Prokaryotic Expression System

Fasciola gigantica cathepsin (cysteine) proteases are potential diagnostic antigens for animal and human fasciolosis. These include cathepsin-L proteases that have been exploited in the diagnosis of animal fasciolosis. However, no scientific data on the diagnostic potential of F. gigantica cathepsin B proteases is available. Therefore, three recombinant antigens of F. gigantica viz. cathepsin (cat) B-1, cat B-2 and cat B-3 were expressed in prokaryotic expression system. The recombinant antigens were purified under denaturing conditions by Nickel affinity chromatography and an optimal level of the recombinant proteins was obtained. These recombinant proteins will further be evaluated for their potential in the early prepatent diagnosis of F. gigantica infection in domestic ruminants.

scholarly journals Cathepsin B Homologue at the Interface between a Parasitic Nematode and Its Intermediate Host

2006 ◽  
Vol 74 (2) ◽  
pp. 1297-1304 ◽  
Author(s):  
Michael S. Duffy ◽  
Deanne K. Cevasco ◽  
Dante S. Zarlenga ◽  
Woraporn Sukhumavasi ◽  
Judith A. Appleton
Keyword(s):  
Intermediate Host ◽  
Cathepsin B ◽  
Parasitic Nematode ◽  
Cysteine Proteases ◽  
Chronic Infections ◽  
Larval Stages ◽  
Snail Intermediate Host ◽  
Putative Active Site ◽  
Domestic Livestock ◽  
Host Tissues

ABSTRACT Parelaphostrongylus tenuis is a parasitic nematode that causes a debilitating neurologic disease in many North American cervids and domestic livestock species. We produced a PCR-based cDNA library from infective larvae (L3) in order to identify molecules that mediate parasitism. A dominant 1,250-bp amplicon encoded a homologue of cathepsin B cysteine proteases. The sequence incorporated a C29G substitution in the putative active site. Antibodies generated against a recombinant form detected the native protein (PtCPR-1) in Western blot assays of L3, but not adult worm, extracts. Immunohistochemical methods revealed that PtCPR-1 synthesis was restricted to larval stages within the snail intermediate host (Triodopsis sp.), beginning as early as 2 days postinfection (dpi) of snails. The protein was present in the intestine and luminal contents and was lost from larvae over time. Concurrent studies showed that larvae induced an immune response in snails beginning at 1 dpi. Layers of hemocytes encapsulated larvae immediately after infection, and granuloma-like structures formed around parasites in chronic infections. Loss of PtCPR-1 from L3 and its accumulation in host tissues coincided with degeneration of granuloma architecture 90 to 105 dpi. Fully developed L3 emerged from the snail at this time. Our data implicate PtCPR-1 in larval development and possibly in the emergence of P. tenuis from the intermediate host. Emerged L3 survived desiccation and cold stress, suggesting that they could remain infectious in the environment. Molecules promoting emergence would facilitate dispersal of L3 and increase the likelihood of transmission to definitive hosts.

scholarly journals Molecular and Biochemical Characterization of a Cathepsin B-Like Protease Family Unique to Trypanosoma congolense

2008 ◽  
Vol 7 (4) ◽  
pp. 684-697 ◽  
Author(s):  
Carlos Mendoza-Palomares ◽  
Nicolas Biteau ◽  
Christiane Giroud ◽  
Virginie Coustou ◽  
Theresa Coetzer ◽  
...  
Keyword(s):  
Cathepsin B ◽  
Biochemical Characterization ◽  
Catalytic Domain ◽  
Expression Profiles ◽  
Specific Inhibitor ◽  
Cysteine Proteases ◽  
Catalytic Triad ◽  
Trypanosoma Congolense

ABSTRACT Cysteine proteases have been shown to be essential virulence factors and drug targets in trypanosomatids and an attractive antidisease vaccine candidate for Trypanosoma congolense. Here, we describe an important amplification of genes encoding cathepsin B-like proteases unique to T. congolense. More than 13 different genes were identified, whereas only one or two highly homologous genes have been identified in other trypanosomatids. These proteases grouped into three evolutionary clusters: TcoCBc1 to TcoCBc5 and TcoCBc6, which possess the classical catalytic triad (Cys, His, and Asn), and TcoCBs7 to TcoCBs13, which contains an unusual catalytic site (Ser, Xaa, and Asn). Expression profiles showed that members of the TcoCBc1 to TcoCBc5 and the TcoCBs7 to TcoCBs13 groups are expressed mainly in bloodstream forms and localize in the lysosomal compartment. The expression of recombinant representatives of each group (TcoCB1, TcoCB6, and TcoCB12) as proenzymes showed that TcoCBc1 and TcoCBc6 are able to autocatalyze their maturation 21 and 31 residues, respectively, upstream of the predicted start of the catalytic domain. Both displayed a carboxydipeptidase function, while only TcoCBc1 behaved as an endopeptidase. TcoCBc1 exhibited biochemical differences regarding inhibitor sensitivity compared to that of other cathepsin B-like proteases. Recombinant pro-TcoCBs12 did not automature in vitro, and the pepsin-matured enzyme was inactive in tests with cathepsin B fluorogenic substrates. In vivo inhibition studies using CA074Me (a cell-permeable cathepsin B-specific inhibitor) demonstrated that TcoCB are involved in lysosomal protein degradation essential for survival in bloodstream form. Furthermore, TcoCBc1 elicited an important immune response in experimentally infected cattle. We propose this family of proteins as a potential therapeutic target and as a plausible antigen for T. congolense diagnosis.

Upregulation of Cathepsin B-like Protease Activity During Apoptosis inGiardia duodenalis

2019 ◽  
Vol 16 (4) ◽  
pp. 330-337
Author(s):  
Sergio Alonso Durán-Pérez ◽  
Héctor Samuel López-Moreno ◽  
Maribel Jiménez-Edeza ◽  
Jesús Ricardo Parra-Unda ◽  
Edgar Rangel-López ◽  
...  
Keyword(s):  
Cell Death ◽  
Dna Fragmentation ◽  
In Silico ◽  
Cathepsin B ◽  
Giardia Duodenalis ◽  
Cysteine Proteases ◽  
Inhibitory Effect ◽  
Death Process ◽  
Catalytic Active Site ◽  
Parasite Survival

Background:In eukaryotic cells, apoptosis signaling pathways are controlled mainly by aspartic acid cysteine proteases (caspases). However, certain unicellular microorganisms, such as Giardia duodenalis, lack these proteins. Thus, other cysteine proteases may play an important role in the parasite apoptosis signaling pathway.Objective:To understand the effect of cathepsin B-like inhibition on the cell viability of Giardia duodenalis and its cell death process.Methods:Bioinformatics analysis was performed to identify apoptotic proteases. Analysis showed that cathepsin B-like protease genes from G. duodenalis were the best candidate. A homology modeling technique was used to explore in silico the inhibitory effect of E-64 against cathepsin B-like proteases from G. duodenalis genome and to examine the effect of curcumin on cathepsin B-like activity regulation. In addition, the effect of E-64 on parasite survival and DNA fragmentation was tested.Results:Eight cathepsin B-like protease coding genes were identified in silico. Interestingly, while these sequences lacked the cathepsin B characteristic occluding loop, they maintained the catalytic active- site responsible for cathepsin B activity, which was evidenced by the increase in the degradation of the Z-RR-AMC substrate, suggesting the upregulation of the activity of these proteins. Additionally, inhibition of E-64 against G. duodenalis trophozoites caused a decrease in DNA fragmentation compared to control cells and had a positive effect on parasite survival after exposure to curcumin.Conclusion:Overall, these results suggested that Giardia duodenalis might have a cell death mechanism in which cathepsin B-like proteases play an important role.

scholarly journals Giardia cathepsin B cysteine proteases degrade interleukin‐8 and attenuate interleukin‐8‐induced neutrophil chemotaxis (152.2)

2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
James Cotton ◽  
Amol Bhargava ◽  
Jose Ferraz ◽  
Robin Yates ◽  
Paul Beck ◽  
...  
Keyword(s):  
Cathepsin B ◽  
Cysteine Proteases ◽  
Interleukin 8 ◽  
Neutrophil Chemotaxis
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