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Kyung-Min Yang, Eunjin Bae, Sung Gwe Ahn, Kyoungwha Pang, Yuna Park, Jinah Park, Jihee Lee, Akira Ooshima, Bora Park, Junil Kim, Yunshin Jung, Satoru Takahashi, Joon Jeong, Seok Hee Park, Seong-Jin Kim
Triple-negative breast cancer (TNBC) is considered incurable with currently available treatments, highlighting the need for therapeutic targets and predictive biomarkers. Here, we report a unique role for Bcl-2-associated athanogene 2 (BAG2), which is significantly overexpressed in TNBC, in regulating the dual functions of cathepsin B as either a pro- or anti-oncogenic enzyme. Silencing BAG2 suppresses tumorigenesis and lung metastasis and induces apoptosis by increasing the intracellular mature form of cathepsin B, whereas BAG2 expression induces metastasis by blocking the auto-cleavage processing of pro-cathepsin B via interaction with the propeptide region...
December 5, 2017: Cell Reports
Georg Nübling, M Schuberth, K Feldmer, A Giese, L M Holdt, D Teupser, S Lorenzl
Limited cleavage promotes the aggregation propensity of protein tau in neurodegenerative tauopathies. Cathepsin S (CatS) is overexpressed in brains of patients suffering from tauopathies such as Alzheimer's disease (AD). Furthermore, CatS serum levels correlate with survival in the elderly. The current study investigates whether limited cleavage by CatS promotes tau aggregation, and whether CatS serum levels may correlate with disease severity in tauopathies. Oligomer formation of fluorescently labeled protein tau was monitored by single particle fluorescence spectroscopy after coincubation with CatS...
August 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
Jingjing Cai, Hong Yuan, Huan Yang, Timothy R Billiar, Alex F Chen
OBJECTIVE: The mechanism of sterile inflammatory response drive the development of vessle remodeling and intimal hyperplasia (IH) was not fully understood. We hypothesis that myeloid differentiation protein-88 (MyD88) in macrophages, the major endocellular adaptor molecule that mediate most toll like receptors (TLRs) induced inflammation, activates processes leading to vessle remodeling via upregulation of cathepsin L activity. DESIGN AND METHOD: Carotid artery wire injury was applied in C57BL/6 wild type (WT) mice, MyD88 mice, Lyz-MyD88 mice and cathepsin L mice to investigate vessel remodeling and intimal formation...
September 2016: Journal of Hypertension
Jingjing Cai, Hong Yuan, Huan Yang, Timothy R Billiar, Alex F Chen
OBJECTIVE: The mechanism of sterile inflammatory response drive the development of vessle remodeling and intimal hyperplasia (IH) was not fully understood. We hypothesis that myeloid differentiation protein-88 (MyD88) in macrophages, the major endocellular adaptor molecule that mediate most toll like receptors (TLRs) induced inflammation, activates processes leading to vessle remodeling via upregulation of cathepsin L activity. DESIGN AND METHOD: Carotid artery wire injury was applied in C57BL/6 wild type (WT) mice, MyD88 mice, Lyz-MyD88 mice and cathepsin L mice to investigate vessel remodeling and intimal formation...
September 2016: Journal of Hypertension
Claudius Luziga, Bui Thi To Nga, Gabriel Mbassa, Yoshimi Yamamoto
Cathepsins B and L are two prominent members of cystein proteases with broad substrate specificity and are known to be involved in the process of intra- and extra-cellular protein degradation and turnover. The propeptide region of cathepsin L is identical to Cytotoxic T-lymphocyte antigen-2α (CTLA-2α) discovered in mouse activated T-cells and mast cells. CTLA-2α exhibits selective inhibitory activities against papain and cathepsin L. We previously demonstrated the distribution pattern of the CTLA-2α protein in mouse brain by immunohistochemistry, describing that it is preferentially localized within nerve fibre bundles than neuronal cell bodies...
September 2016: Acta Histochemica
Kate A Redgrove, Eileen A McLaughlin
Chlamydia trachomatis (CT) is the most prevalent bacterial sexually transmitted infection in the world, with more than 100 million cases reported annually. While there have been extensive studies into the adverse effects that CT infection has on the female genital tract, and on the subsequent ability of these women to conceive, studies into the consequences on male fertility have been limited and controversial. This is in part due to the asymptomatic nature of the infection, where it is estimated that 50% of men with Chlamydia fail to show any symptoms...
2014: Frontiers in Immunology
Li Zhang, Handong Wang, Jianguo Xu, Jianhong Zhu, Ke Ding
Cathepsin S is a lysosomal cysteine protease that is overexpressed in various cancer models and plays important role in tumorigenesis, however the mechanisms are unclear. In the present study, we found that inhibition of cathepsin S induced autophagy and mitochondrial apoptosis in human glioblastoma cells. Blockade of autophagy by either a chemical inhibitor or RNA interference attenuated cathespin S inhibition-induced apoptosis. Furthermore, autophagy and apoptosis induction was dependent on the suppression of phosphatidylinositide 3-kinases/protein kinase B/mammalian target of rapamycin/p70S6 kinase (PI3K/AKT/mTOR/p70S6K) signaling pathway and activation of c-Jun N-terminal kinase (JNK) signaling pathway...
August 4, 2014: Toxicology Letters
A Ouali, N Garrel, A Obled, C Deval, C Valin, I F Penny
Specific action of cathespins D, B, H, L, and of a new high Mr (molecular weight relative to hydrogen) cysteine proteinase, on rabbit muscle myofibrils was studied at pH 5·7 by following changes affecting their ATPase activities, their calcium sensitivity, their effect on the ultrastructure, as well as the electrophoretic pattern of the contractile proteins in the presence of SDS. With regard to the MgCa-enhanced ATPase activity, all these proteinases had a very similar effect. A decrease in this activity was thus noted concomitantly with a shift of the straight-line graph obtained when plotting the present acto-myosin ATPase activity versus KCl concentrations...
1987: Meat Science
Nermin Yamalik, Sevim Günday, Kamer Kilinc, Erdem Karabulut, Ezel Berker, Tolga F Tözüm
PURPOSE: Cathepsin-K is an enzyme involved in bone metabolism. This feature may make it important both for natural teeth and dental implants. The aims of the present study were to comparatively analyze cathepsin-K levels in gingival crevicular fluid (GCF) and peri-implant sulcus fluid (PISF) and to determine whether GCF and PISF cathepsin-K profiles reflect the clinical periodontal/peri-implant status. MATERIALS AND METHODS: Clinical parameters (probing depth, Gingival Index, Plaque Index, and bleeding on probing) were recorded, and GCF/PISF samples were obtained from natural teeth (group T) and dental implants (group I), which were divided into groups based on health (clinically healthy, gingivitis/peri-implant mucositis, and periodontitis/peri-implantitis)...
September 2011: International Journal of Oral & Maxillofacial Implants
Jessica Ingram, Giselle Knudsen, K C Lim, Elizabeth Hansell, Judy Sakanari, James McKerrow
BACKGROUND: Skin invasion is the initial step in infection of the human host by schistosome blood flukes. Schistosome larvae have the remarkable ability to overcome the physical and biochemical barriers present in skin in the absence of any mechanical trauma. While a serine peptidase with activity against insoluble elastin appears to be essential for this process in one species of schistosomes, Schistosoma mansoni, it is unknown whether other schistosome species use the same peptidase to facilitate entry into their hosts...
September 2011: PLoS Neglected Tropical Diseases
Wan-Yu Hsieh, Cheng-Chung Chou, Chao-Chi Ho, Sung-Liang Yu, Hsuan-Yu Chen, Han-Yi E Chou, Jeremy J W Chen, Huei-Wen Chen, Pan-Chyr Yang
Inhalation of single-walled carbon nanotubes (SWCNTs) has raised serious concerns related to potential toxic effects in the respiratory system. This study examined possible SWCNT-induced toxic mechanisms in vivo in mice. The results indicated that a single intratracheal instillation of SWCNTs could induce airway hyperreactivity and airflow obstruction and confirmed previous findings of granulomatous changes in the lung parenchyma that persisted from 7 days to 6 months after exposure. The irreversible lung pathology and functional airway alterations in the mouse model mimicked obstructive airway disease in humans...
February 2012: American Journal of Respiratory Cell and Molecular Biology
Kelem Kassahun, W Cameron Black, Deborah Nicoll-Griffith, Ian McIntosh, Nathalie Chauret, Stephen Day, Elizabeth Rosenberg, Kenneth Koeplinger
Odanacatib is a potent cathespin K inhibitor that is being developed as a novel therapy for osteoporosis. The disposition and metabolism of odanacatib were evaluated in rats, dogs, and rhesus monkeys after intravenous and oral administration of [¹⁴C]odanacatib. Odanacatib was characterized by low systemic clearance in all species and by a long plasma half-life in monkeys (18 h) and dogs (64 h). The oral bioavailability was dependent on the vehicle used and ranged from 18% (monkey) to ~100% (dog) at doses of 1 to 5 mg/kg, using nonaqueous vehicles...
June 2011: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Krishna Kumar Veeravalli, Chandramu Chetty, Shivani Ponnala, Christopher S Gondi, Sajani S Lakka, Daniel Fassett, Jeffrey D Klopfenstein, Dzung H Dinh, Meena Gujrati, Jasti S Rao
BACKGROUND: Involvement of MMP-9, uPAR and cathepsin B in adhesion, migration, invasion, proliferation, metastasis and tumor growth has been well established. In the present study, MMP-9, uPAR and cathepsin B genes were downregulated in glioma xenograft cells using shRNA plasmid constructs and we evaluated the involvement of integrins and changes in their adhesion, migration and invasive potential. METHODOLOGY/PRINCIPAL FINDINGS: MMP-9, uPAR and cathepsin B single shRNA plasmid constructs were used to downregulate these molecules in xenograft cells...
July 15, 2010: PloS One
Chong Zhang, Jia-bang Sun, Da-chuan Liu, Ye-qing Cui, Shuang Liu, Hai-chen Sun
BACKGROUND: Cathespin-B (cath-B) is an important proteolytic enzyme involved in the disease course of invasion in many types of cancer. Cath-B expression in subcutaneous heteroplastic pancreatic carcinoma in nude mice has not been studied. We investigated the role of cath-B in a model of heteroplastic pancreatic carcinoma in BALB/c nude mice. METHODS: Thirty-two six-week-old female BALB/c nude mice were equally divided into four groups. PANC-1 cells were inoculated subcutaneously in the left axillary region...
October 20, 2009: Chinese Medical Journal
Shane Sullivan, Miriam Tosetto, David Kevans, Alan Coss, Laimun Wang, Diarmuid O'Donoghue, John Hyland, Kieran Sheahan, Hugh Mulcahy, Jacintha O'Sullivan
Previous in vitro studies have identified a nuclear isoform of Cathepsin L. The aim of this study was to examine if nuclear Cathepsin L exists in vivo and examine its association with clinical, pathological and patient outcome data. Cellular localization (nuclear and cytoplasmic) and expression levels v of Cathespin L in 186 colorectal cancer cases using immunohistochemistry. The molecular weight and activity of nuclear and cytoplasmic Cathepsin L in vivo and in vitro were assessed by Western blotting and ELISA, respectively...
July 1, 2009: International Journal of Cancer. Journal International du Cancer
Sinéad Nic An Ultaigh, James C Carolan, Collette Britton, Linda Murray, Michael F Ryan
Cathespin L-like proteases (CPLs), characterized from a wide range of helminths, are significant in helminth biology. For example, in Caenorhabditis elegans CPL is essential for embryogenesis. Here, we report a cathepsin L-like gene from three species of strongyles that parasitize the horse, and describe the isolation of a cpl gene (Sv-cpl-1) from Strongylus vulgaris, the first such from equine strongyles. It encodes a protein of 354 amino acids with high similarity to other parasitic Strongylida (90-91%), and C...
April 2009: Experimental Parasitology
P Björk, T Gudmundsson, K Ohlsson
In this work we have studied the acute phase protein response and degranulation of polymorphonuclear leukocytes in vivo in the rat after a slow interleukin-1beta stimulation. A total dose of 1 mug, 2 mug, 4 mug and 0 mug (controls with only vehicle) of interleukin-1beta was released from osmotic minipumps over a period of 7 days. The pumps were implanted subcutaneously. A cystic formation was formed around the pumps that contained interleukin-1beta whereas no tissue reaction was seen around pumps containing only vehicle...
1994: Mediators of Inflammation
Maria Cristina Honorati, Luca Cattini, Andrea Facchini
We compared the secretion of vascular endothelial growth factor (VEGF) by chondrocytes isolated from cartilage of patients with osteoarthritis (OA) and maintained in monolayer or in three-dimensional culture. Chondrocytes, immediately after isolation, or after one passage in monolayer culture (subculture), were seeded in monolayer or pelleted in micromasses. Cells cultured differently were immunoassayed for the secretion of VEGF in basal conditions or after stimulation with IL-17, TNF-alpha or B IL-17+TNF-alpha...
2007: Connective Tissue Research
Jining Lü, Jun Qian, Daniel Keppler, Wellington V Cardoso
During lung development, signaling by Fgf10 (fibroblast growth factor 10) and its receptor Fgfr2b is critical for induction of a gene network that controls proliferation, differentiation, and branching of the epithelial tubules. The downstream events triggered by Fgf10-Fgfr2b signaling during this process are still poorly understood. In a global screen for transcriptional targets of Fgf10, we identified Ctsh (cathepsin H), a gene encoding a lysosomal cysteine protease of the papain family, highly up-regulated in the developing lung epithelium...
July 27, 2007: Journal of Biological Chemistry
Shin-Rong Hwang, Christina Garza, Charles Mosier, Thomas Toneff, Eric Wunderlich, Paul Goldsmith, Vivian Hook
Proteases within secretory vesicles are required for conversion of neuropeptide precursors into active peptide neurotransmitters and hormones. This study demonstrates the novel cellular role of the cysteine protease cathepsin L for producing the (Met)enkephalin peptide neurotransmitter from proenkephalin (PE) in the regulated secretory pathway of neuroendocrine PC12 cells. These findings were achieved by coexpression of PE and cathepsin L cDNAs in PC12 cells with analyses of PE-derived peptide products. Expression of cathepsin L resulted in highly increased cellular levels of (Met)enkephalin, resulting from the conversion of PE to enkephalin-containing intermediates of 23, 18-19, 8-9, and 4...
March 30, 2007: Journal of Biological Chemistry
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