Cigarette smoke stimulates cathepsin B activity in alveolar macrophages of rats.
ABSTRACT Cathepsin B activity was determined in alveolar macrophages and cell-free bronchoalveolar lavage fluid from Sprague-Dawley rats exposed only through the nose to fresh mainstream smoke from University of Kentucky high-tar, high-nicotine reference cigarettes, and in cells and fluid from room control and sham control animals. Increased levels of blood carboxyhemoglobin and pulmonary aryl hydrocarbon hydroxylase activity in smoke-exposed animals indicated effective exposure of animals to cigarette smoke. Cathepsin B activity was quantitated with alpha-N-benzyloxycarbonyl-leucine-leucine-arginine-2-naphthylamide as substrate. Specific activity (nanomoles of substrate cleaved per milligram of protein per hour) in alveolar macrophages was increased by 43% at both 4- and 10-week exposure points in animals exposed twice daily to 10 puffs of cigarette smoke. These data indicate that maximal stimulation of the enzyme occurs within 4 weeks of the initiation of smoke exposure. When the activity was expressed on a per-cell basis, cathepsin B activity was also increased in the smoke-exposed group at both exposure points. Activity in bronchoalveolar lavage fluid of smoke-exposed animals was increased by approximately 50% at 4 and 10 weeks, but the differences were not statistically significant. These findings demonstrate that cigarette smoke is a potent inducer of cathepsin B activity in alveolar macrophages of rats.
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ABSTRACT: In order to evaluate the role of cysteine peptidase cathepsin H (Cath H) in human lung cancer its protein levels were determined in 148 pairs of lung tumour tissue and adjacent non-tumourous lung parenchyma using the enzyme-linked immunosorbent assay technique. Additionally, Cath H levels were determined in sera of 171 patients with malignant tumours, 34 patients with benign lung diseases and 47 healthy controls. The median level of Cath H in tumour tissue was 0.64 times that in the corresponding lung parenchyma. Relating tumour levels with histological type we found higher Cath H levels in small-cell and adenocarcinomas and lower levels in squamous cell carcinoma, large-cell carcinoma and secondary tumours. A significant difference in Cath H level between lung tumour tissue and non-tumourous lung parenchyma was associated with the group of cigarette smokers (156 vs 263 ng mg(-1) protein, P < 0.001). For this group of patients Cath H tumour levels correlated with the survival rate, while for the entire patient population this was not the case. Smokers with high tumour levels of Cath H experienced poor survival. Cath H was significantly higher in sera of patients with malignant and benign lung diseases than in control sera (P < 0.001). The increase was significant for all histological types, being the highest in small-cell and squamous cell carcinomas. Our study reveals that in lung tumours there is different behaviour of Cath H compared with other cysteine peptidases, e.g. cathepsin B and cathepsin L. Variations between tissue and serum levels of Cath H indicate either reduced expression or enhanced secretion of this enzyme in lung tumours.British Journal of Cancer 02/2000; 82(4):782-8. · 5.08 Impact Factor
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ABSTRACT: Cigarette smoke, which contains several carcinogens known to initiate and promote tumorigenesis and metastasis, is the major cause of oral cancer. Lysosomal cathepsin proteases play important roles in tumor progression, invasion and metastasis. In the present work we investigated the effects of cigarette smoke condensate (CSC) on cathepsin (B, D and L) expression and protease-mediated invasiveness in human oral squamous cell carcinoma (OSCC) cells. Our results show that treatment of OSCC cells (686Tu and 101A) with CSC activated cathepsins B, D and L in a dose-dependent manner. Both expression and activity of these cathepsins were up-regulated in CSC-exposed versus non-exposed cells. Although cathepsin L had the lowest basal level, it had the highest induction in exposed cells compared to cathepsins B and D. Suppression of CSC-induced cathepsin B and L activities by specific chemical inhibitors decreased the invasion process, suggesting that these proteases are involved in the invasion process. Overall, our results indicate that CSC activates cathepsin B and L proteolytic activity and enhances invasiveness in OSCC cells, a response that may play a role in CSC-mediated tumor progression and metastasis dissemination.Toxicology Letters 04/2007; 170(2):134-45. · 3.15 Impact Factor
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ABSTRACT: Indiana Geological Survey Circular 7 Fossils are abundant in Indiana’s rocks, and Hoosiers commonly seek information about these relics of ancient life from the Indiana Geological Survey. The primary purpose of this circular is to provide information on the principles of paleontology and the major kinds of fossils found in Indiana. Many of the fossils illustrated in this Circular are found in Indiana bedrock; some have been included to provide more information on the characteristics of the major groups of fossils. Another purpose is to stimulate interest in fossil collecting, a healthful pastime that may lead younger readers to a rewarding career. This account of ancient life concludes with a list of books that deal largely with fossils and earth history. Fossilized remains of primitive vertebrates are not discussed as they are rare in Hoosier rocks. Prehistoric plant life in Indiana is not considered, as Canright (1959) has recently described plants that grew in Indiana in the geologic past. Indiana Department of Conservation