Intracellular proteolytic activity of cathepsin B is associated with capillary‐like tube formation by endothelial cells in vitro

Premzl, Aleš; Türk, Vito; Kos, Janko

doi:10.1002/jcb.20720

Cited by 57 publications

(43 citation statements)

References 48 publications

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“…Treatment of cells with membrane-permeable CA-074Me effectively abolished intracellular CB activity, which is implicated in the degradation of ECM. 48 CA-074Me conferred a protective effect in OA-induced cell apoptosis and reduced amyloid precursor protein accumulation and a-spectrin cleavage in Alzheimer's disease. 49 In previous study, specific CB inhibitor CA-074Me attenuated the expression of CB in the development of ischemic astrocytic cell death both in in vivo and in vitro ischemic models.…”

Section: Discussionmentioning

confidence: 93%

Treatment with CA-074Me, a Cathepsin B inhibitor, reduces lung interstitial inflammation and fibrosis in a rat model of polymyositis

Zhang

et al. 2015

Laboratory Investigation

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Cathepsin B (CB) is involved in the turnover of proteins and has various roles in maintaining the normal metabolism of cells. In our recent study, CB is increased in the muscles of polymyositis/dermatomyositis (PM/DM). However, the role of CB in interstitial lung disease (ILD) has not been reported. ILD is a frequent complication of PM/DM, which is the leading cause of death in PM/DM. It carries high morbidity and mortality in connective tissue diseases, characterized by an overproduction of inflammatory cytokines and induced fibrosis, resulting in respiratory failure. The etiology and pathogenesis of ILD remain incompletely understood. This study investigated whether treatment with CA-074Me, a specific inhibitor of CB, attenuates ILD in PM. CB expression, inflammation, and fibrosis were analyzed in the lung tissues from patients with PM/DM. The animal model of PM was induced in guinea pigs with Coxsackie virus B1 (CVB1). CA-074Me was given 24 h after CVB1 injection for 7 consecutive days. At the end of the experiment, the animals were killed and lung tissues were collected for the following analysis. Inflammation, fibrosis and apoptosis cells, and cytokines were assessed by histological examinations and immunohistochemical analyses, western blot analysis and transferasemediated dUTP nick-end labeling assay. In patients with PM/DM, the protein levels of CB were significantly elevated in lung tissues compared with healthy controls, which correlated with increases in inflammation and fibrosis. Similarly, the expression of CB, inflammation and fibrosis, CD8 þ T cell, CD68 þ cell, tumor necrosis factor-alpha, transforming growth factor-beta1 infiltrations, and apoptotic cell death were significantly increased in lung tissues of the guinea-pig model of CVB1-induced PM. These changes were attenuated by the administration of CA-074Me. In conclusion, this study demonstrates that PM/DM increases CB expression in lung tissues and inhibition of CB reduces ILD in a guinea-pig model of CVB1-induced PM. This finding suggests that CB may be a potential therapeutic target for ILD.

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Section: Discussionmentioning

confidence: 93%

Treatment with CA-074Me, a Cathepsin B inhibitor, reduces lung interstitial inflammation and fibrosis in a rat model of polymyositis

Zhang

et al. 2015

Laboratory Investigation

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“…Therefore, researchers have proposed that cathepsin B plays critical roles in the invasion and metastasis of cancers (16)(17)(18). Research demonstrated that the expression and activity of these enzymes are related to cancer stage and metastasis and that these enzymes may be used as predictors (7).…”

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confidence: 99%

Expression and clinical significance of cathepsin B and stefin A in laryngeal cancer

Chen²,

Wang³

et al. 2011

Oncol Rep

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Abstract. The aim of this study was to investigate the roles of the cathepsin B cysteine protease and its endogenous inhibitor stefin A in laryngeal cancer. Immunohistochemistry was employed to detect the expression of cathepsin B and stefin A in 84 patients with laryngeal cancer, respectively. The protein expression of stefin A was negatively associated with lymphatic metastasis, recurrence of laryngeal cancer and the survival rate, which was not observed with cathepsin B protein expression. Both down-regulation of cathepsin B and up-regulation of stefin A in vitro significantly inhibited the migration, invasion and proliferation of laryngeal cancer cells, respectively. Our results strongly suggest that stefin A may be a potential predictor of laryngeal cancer and may be used in the molecular diagnosis and gene therapy of laryngeal cancer. Cathepsin B may be used as a promising therapeutic target in the treatment of laryngeal cancer. IntroductionLaryngeal cancer is a common head and neck malignancy and accounts for 7% of all malignancies, and the incidence of laryngeal cancer has been increasing over the years. Laryngeal cancer is associated with a high prevalence of local invasion and cervical lymph node metastasis, and a majority of patients die of cervical recurrence and metastasis. Investigations concerning the invasion and metastasis of laryngeal cancer may clarify the exact mechanisms underlying these processes and may identify novel therapeutic targets. The invasion and metastasis of cancers are complex, multistep, multifactor interacting, and dynamic biological processes involving cancer cells, host cells and the extracellular matrix (1). Invasion is a prerequisite of metastasis that depends on adherence and degradation of the extracellular matrix by degradative enzymes (2). Liotta et al proposed that the invasion and metastasis of cancers involve three steps: i) adherence between cancer cells and the extracellular matrix; ii) the release of proteolytic enzymes causing the degradation of the extracellular matrix; and iii) migration of cancer cells under the action of chemokines. This theory suggests that adherence, degradation and migration act sequentially and repetitively, ultimately resulting in sustained invasion and distal metastasis of cancer cells (3). The impairment of the basement membrane has been considered an important marker of cancer invasion, and the degradation of the extracellular matrix by proteolytic enzymes is a critical step of invasion and metastasis of cancer cells. Based on the substrates and pH values for enzyme catalysis, proteolytic enzymes can be classified into four types: serine proteases, matrix metalloproteinases, cysteine proteases, and aspartic proteases. These proteases have different biological functions related to cancer and play an important role in the occurrence, invasion, angiogenesis, and metastasis of cancers. Cancer invasion depends on the local concentration of proteases and the balance between proteases and their inhibitors. Under normal conditions, protease...

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“…Uncleaved cresyl violet substrates show an emission peak at 570 nm when excited at 540 nm, and cleaved cresyl violet has an emission peak at 628 nm when excited at 540 nm ( Figure 5) (Boonacker et al 2003a). The activity can be imaged using confocal laser scanning microscopy (Boonacker et al 2002(Boonacker et al ,2003aPremzl et al 2006) and measured per individual cell using flow cytometry (Creasy et al 2007). In the latter study, activity of cathepsin B, L, and S was combined with immunofluorescence staining of leukocytes to detect cell lineage-specific activity in heterogeneous cell populations (Creasy et al 2007).…”

Section: Magic Red Substrates the Cresyl Violet-based Magicmentioning

confidence: 99%

Imaging Enzymes at Work: Metabolic Mapping by Enzyme Histochemistry

Noorden

2010

J Histochem Cytochem.

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S U M M A R Y For the understanding of functions of proteins in biological and pathological processes, reporter molecules such as fluorescent proteins have become indispensable tools for visualizing the location of these proteins in intact animals, tissues, and cells. For enzymes, imaging their activity also provides information on their function or functions, which does not necessarily correlate with their location. Metabolic mapping enables imaging of activity of enzymes. The enzyme under study forms a reaction product that is fluorescent or colored by conversion of either a fluorogenic or chromogenic substrate or a fluorescent substrate with different spectral characteristics. Most chromogenic staining methods were developed in the latter half of the twentieth century but still find new applications in modern cell biology and pathology. Fluorescence methods have rapidly evolved during the last decade. This review critically evaluates the methods that are available at present for metabolic mapping in living animals, unfixed cryostat sections of tissues, and living cells, and refers to protocols of the methods of choice. (J Histochem Cytochem 58:481-497, 2010)

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Intracellular proteolytic activity of cathepsin B is associated with capillary‐like tube formation by endothelial cells in vitro

Cited by 57 publications

References 48 publications

Treatment with CA-074Me, a Cathepsin B inhibitor, reduces lung interstitial inflammation and fibrosis in a rat model of polymyositis

Treatment with CA-074Me, a Cathepsin B inhibitor, reduces lung interstitial inflammation and fibrosis in a rat model of polymyositis

Expression and clinical significance of cathepsin B and stefin A in laryngeal cancer

Imaging Enzymes at Work: Metabolic Mapping by Enzyme Histochemistry

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