scholarly journals In Vitro Antibacterial Activity of Cysteine Protease Inhibitor from Kiwifruit (Actinidia deliciosa)

2012 ◽  
Vol 53 (1) ◽  
pp. 100-105 ◽  
Author(s):  
Milica Popovic ◽  
Uros Andjelkovic ◽  
Milica Grozdanovic ◽  
Ivana Aleksic ◽  
Marija Gavrovic-Jankulovic
Keyword(s):  
Antibacterial Activity ◽  
Protease Inhibitor ◽  
Cysteine Protease ◽  
Actinidia Deliciosa ◽  
Cysteine Protease Inhibitor ◽  
In Vitro Antibacterial Activity

scholarly journals Effect of phenyl vinyl sulphone cysteine protease inhibitor on Schistosoma mansoni: in vitro and in vivo experimental studies

2017 ◽  
Vol 41 (4) ◽  
pp. 1049-1058
Author(s):  
Manal Salah El-Din Mahmoud ◽  
Ayman Nabil Ibrahim ◽  
Abeer Fathy Badawy ◽  
Nourhan Mohamed Abdelmoniem
Keyword(s):  
Protease Inhibitor ◽  
Schistosoma Mansoni ◽  
Cysteine Protease ◽  
Experimental Studies ◽  
Cysteine Protease Inhibitor ◽  
Phenyl Vinyl

A protein extract and a cysteine protease inhibitor enriched fraction from Jatropha curcas seed cake have in vitro anti-Toxoplasma gondii activity

2015 ◽  
Vol 153 ◽  
pp. 111-117 ◽  
Author(s):  
A.M.S. Soares ◽  
L.P. Carvalho ◽  
E.J.T. Melo ◽  
H.P.S. Costa ◽  
I.M. Vasconcelos ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Protease Inhibitor ◽  
Cysteine Protease ◽  
Jatropha Curcas ◽  
Cysteine Protease Inhibitor ◽  
Protein Extract ◽  
Seed Cake

scholarly journals A Phytophthora palmivora Extracellular Cystatin-Like Protease Inhibitor Targets Papain to Contribute to Virulence on Papaya

2018 ◽  
Vol 31 (3) ◽  
pp. 363-373 ◽  
Author(s):  
Rebecca Gumtow ◽  
Dongliang Wu ◽  
Janice Uchida ◽  
Miaoying Tian
Keyword(s):  
Protease Inhibitor ◽  
Protease Inhibitors ◽  
Cysteine Protease ◽  
Gene Editing ◽  
Sequence Data ◽  
Cysteine Protease Inhibitor ◽  
Phytophthora Palmivora ◽  
Cysteine Protease Inhibitors ◽  
Successful Infection

Papaya fruits, stems, and leaves are rich in papain, a cysteine protease that has been shown to mediate plant defense against pathogens and insects. Yet the oomycete Phytophthora palmivora is a destructive pathogen that infects all parts of papaya plants, suggesting that it has evolved cysteine protease inhibitors to inhibit papain to enable successful infection. Out of five putative extracellular cystatin-like cysteine protease inhibitors (PpalEPICs) from P. palmivora transcriptomic sequence data, PpalEPIC8 appeared to be unique to P. palmivora and was highly induced during infection of papaya. Purified recombinant PpalEPIC8 strongly inhibited papain enzyme activity, suggesting that it is a functional cysteine protease inhibitor. Homozygous PpalEPIC8 mutants were generated using CRISPR/Cas9-mediated gene editing via Agrobacterium-mediated transformation (AMT). Increased papain sensitivity of in-vitro growth and reduced pathogenicity during infection of papaya fruits were observed for the mutants compared with the wild-type strain, suggesting that PpalEPIC8, indeed, plays a role in P. palmivora virulence by inhibiting papain. This study provided genetic evidence demonstrating that plant-pathogenic oomycetes secrete cystatins as important weapons to invade plants. It also established an effective gene-editing system for P. palmivora by the combined use of CRISPR/Cas9 and AMT, which is expected to be applicable to other oomycetes.

scholarly journals Fowlerstefin, a cysteine protease inhibitor of Naegleria fowleri, induces inflammatory responses in BV-2 microglial cells in vitro

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Thị Lam Thái ◽  
Jung-Mi Kang ◽  
Hương Giang Lê ◽  
Jinyoung Lee ◽  
Won Gi Yoo ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
Cysteine Protease ◽  
Inflammatory Responses ◽  
Microglial Cells ◽  
Cysteine Protease Inhibitor ◽  
Naegleria Fowleri ◽  
Nægleria Fowleri

STEM-15. SerpinB3 DRIVES CANCER STEM CELL SURVIVAL IN GLIOBLASTOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi24-vi24
Author(s):  
Adam Lauko ◽  
Soumya M Turaga ◽  
Josephine Volovetz ◽  
Defne Bayik ◽  
Shideng Bao ◽  
...  
Keyword(s):  
Cell Death ◽  
Protease Inhibitor ◽  
Cysteine Protease ◽  
Xenograft Model ◽  
Standard Of Care ◽  
Therapeutic Interventions ◽  
Cysteine Protease Inhibitor ◽  
Orthotopic Xenograft Model

Abstract Despite therapeutic interventions for glioblastoma (GBM), self-renewing, therapy-resistant populations of cells referred to as cancer stem cells (CSCs) drive recurrence. Previously, we identified the unique expression of junctional adhesion molecule-A (JAM-A) on CSCs and demonstrated that JAM-A is both necessary and sufficient for self-renewal and tumor growth. Moreover, we determined that JAM-A signals via Akt in GBM CSCs to sustain pluripotency transcription factor activity; however, the entire signaling network has yet to be fully elucidated. To further delineate this pathway, we immunoprecipitated JAM-A from patient-derived GBM CSCs and performed mass spectrometry to determine JAM-A binding proteins. This led to the identification of the cysteine protease inhibitor SerpinB3 as a putative JAM-A binding partner. Using in vitro CSC functional assays, we show that SerpinB3 is necessary for CSC maintenance and survival. In an in vivo orthotopic xenograft model, knockdown of SerpinB3 extended survival. Mechanistically, knockdown of SerpinB3 led to decreased expression of TGF-β, Myc, WNT, and Notch signaling, known regulators of the CSC state. Additionally, knockdown of SerpinB3 increases susceptibility to radiation therapy. SerpinB3 is essential for buffering cells against cathepsin-mediated cell death, and we found that elevated lysosomal membrane permeability after radiation leads to cathepsin release into the cytoplasm. As a result, SerpinB3 knockdown cells have a diminished capacity to inhibit cathepsin-driven cell death after radiation. The addition of the cathepsin inhibitor E64D partially rescues the SerpinB3 knockdown, however, SerpinB3 mutants that are unable to inhibit cathepsins fail to do the same. Taken together, our findings, identify a novel GBM CSC-specific survival mechanism involving a previously uninvestigated cysteine protease inhibitor, SerpinB3, and provide a potential target to increase the efficacy of standard of care GBM therapies against therapy-resistant CSCs.

scholarly journals In vitro ANTIGIARDIAL ACTIVITY OF THE CYSTEINE PROTEASE INHIBITOR E-64

2014 ◽  
Vol 56 (1) ◽  
pp. 43-47 ◽  
Author(s):  
Thais Batista de Carvalho ◽  
Teresa Cristina Goulart Oliveira-Sequeira ◽  
Semiramis Guimaraes
Keyword(s):  
Protease Inhibitor ◽  
Cysteine Protease ◽  
Cysteine Protease Inhibitor ◽  
Parasite Survival ◽  
Dye Reduction ◽  
Antigiardial Activity ◽  
Host Parasite ◽  
Druggable Targets ◽  
Vitro Effect

The quest for new antiparasitic alternatives has led researchers to base their studies on insights into biology, host-parasite interactions and pathogenesis. In this context, proteases and their inhibitors are focused, respectively, as druggable targets and new therapy alternatives. Herein, we proposed to evaluate the in vitro effect of the cysteine protease inhibitor E-64 on Giardia trophozoites growth, adherence and viability. Trophozoites (105) were exposed to E-64 at different final concentrations, for 24, 48 and 72 h at 37 °C. In the growth and adherence assays, the number of trophozoites was estimated microscopically in a haemocytometer, whereas cell viability was evaluated by a dye-reduction assay using MTT. The E-64 inhibitor showed effect on growth, adherence and viability of trophozoites, however, its better performance was detected in the 100 µM-treated cultures. Although metronidazole was more effective, the E-64 was shown to be able to inhibit growth, adherence and viability rates by ≥ 50%. These results reveal that E-64 can interfere in some crucial processes to the parasite survival and they open perspectives for future investigations in order to confirm the real antigiardial potential of the protease inhibitors.

scholarly journals A Cysteine Protease Inhibitor Rescues Mice from a Lethal Cryptosporidium parvum Infection

2013 ◽  
Vol 57 (12) ◽  
pp. 6063-6073 ◽  
Author(s):  
Momar Ndao ◽  
Milli Nath-Chowdhury ◽  
Mohammed Sajid ◽  
Victoria Marcus ◽  
Susan T. Mashiyama ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
Cryptosporidium Parvum ◽  
Cysteine Protease ◽  
Intestinal Inflammation ◽  
Cysteine Protease Inhibitor ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Content Type ◽  
Mammalian Cell Lines

ABSTRACTCryptosporidiosis, caused by the protozoan parasiteCryptosporidium parvum, can stunt infant growth and can be lethal in immunocompromised individuals. The most widely used drugs for treating cryptosporidiosis are nitazoxanide and paromomycin, although both exhibit limited efficacy. To investigate an alternative approach to therapy, we demonstrate that the clan CA cysteine protease inhibitorN-methyl piperazine-Phe-homoPhe-vinylsulfone phenyl (K11777) inhibitsC. parvumgrowth in mammalian cell lines in a concentration-dependent manner. Further, using the C57BL/6 gamma interferon receptor knockout (IFN-γR-KO) mouse model, which is highly susceptible toC. parvum, oral or intraperitoneal treatment with K11777 for 10 days rescued mice from otherwise lethal infections. Histologic examination of untreated mice showed intestinal inflammation, villous blunting, and abundant intracellular parasite stages. In contrast, K11777-treated mice (210 mg/kg of body weight/day) showed only minimal inflammation and no epithelial changes. Three putative protease targets (termed cryptopains 1 to 3, or CpaCATL-1, -2, and -3) were identified in theC. parvumgenome, but only two are transcribed in infected mammals. A homology model predicted that K11777 would bind to cryptopain 1. Recombinant enzymatically active cryptopain 1 was successfully targeted by K11777 in a competition assay with a labeled active-site-directed probe. K11777 exhibited no toxicityin vitroandin vivo, and surviving animals remained free of parasites 3 weeks after treatment. The discovery that a cysteine protease inhibitor provides potent anticryptosporidial activity in an animal model of infection encourages the investigation and development of this biocide class as a new, and urgently needed, chemotherapy for cryptosporidiosis.

scholarly journals Nippocystatin, a Cysteine Protease Inhibitor fromNippostrongylus brasiliensis, Inhibits Antigen Processing and Modulates Antigen-Specific Immune Response

2001 ◽  
Vol 69 (12) ◽  
pp. 7380-7386 ◽  
Author(s):  
Teruki Dainichi ◽  
Yoichi Maekawa ◽  
Kazunari Ishii ◽  
Tianqian Zhang ◽  
Baher Fawzy Nashed ◽  
...  
Keyword(s):  
Immune System ◽  
Protease Inhibitor ◽  
Cysteine Protease ◽  
Antigen Processing ◽  
Cysteine Proteases ◽  
Cysteine Protease Inhibitor ◽  
Host Immune System ◽  
Nippostrongylus Brasiliensis

ABSTRACT During infection, parasites evade the host immune system by modulating or exploiting the immune system; e.g., they suppress expression of major histocompatibility complex class II molecules or secrete cytokine-like molecules. However, it is not clear whether helminths disturb the immune responses of their hosts by controlling the antigen-processing pathways of the hosts. In this study, we identified a new cysteine protease inhibitor, nippocystatin, derived from excretory-secretory (ES) products of an intestinal nematode,Nippostrongylus brasiliensis. Nippocystatin, which belongs to cystatin family 2, consists of 144 amino acids and is secreted as a 14-kDa mature form. In vivo treatment of ovalbumin (OVA)-immunized mice with recombinant nippocystatin (rNbCys) profoundly suppressed OVA-specific proliferation of splenocytes but not non-antigen-specific proliferation of splenocytes. OVA-specific cytokine production was also greatly suppressed in rNbCys-treated mice. Although the serum levels of both OVA-specific immunoglobulin G1 (IgG1) and IgG2a were not affected by rNbCys treatment, OVA-specific IgE was preferentially downregulated in rNbCys-treated mice. In vitro rNbCys inhibited processing of OVA by lysosomal cysteine proteases from the spleens of mice. Mice with anti-nippocystatin antibodies became partially resistant to infection with N. brasiliensis. Based on these findings, N. brasiliensis appears to skillfully evade host immune systems by secreting nippocystatin, which modulates antigen processing in antigen-presenting cells of hosts.

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