{"title":"Cathepsin B: multiple enzyme forms from a single gene and their relation to cancer.","authors":"D Keppler, B F Sloane","doi":"10.1159/000468619","DOIUrl":"https://doi.org/10.1159/000468619","url":null,"abstract":"<p><p>Overexpression and altered trafficking of cathepsin B characterize the malignant phenotype of tumor cells. Human cathepsin B is encoded by a single-copy gene located on chromosome 8p22. With its 13 exons, the gene encompasses at least 27 kb of DNA. Expression of cathepsin B can be regulated at transcriptional and posttranscriptional levels. Multiple cathepsin B mRNA species arising from alternative splicing may be related to tissue- and tumor-specific differences in expression. There is selective overexpression, increased activity, membrane association and secretion of cathepsin B in many etiologically different cancers. This suggests that cathepsin B may play a functional role in malignant progression. Recent clinical studies provide confirmatory evidence in that cathepsin B expression is a prognostic indicator in colon carcinoma.</p>","PeriodicalId":11854,"journal":{"name":"Enzyme & protein","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000468619","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19766948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Alterations and role of human cathepsin D in cancer metastasis.","authors":"H Rochefort, E Liaudet, M Garcia","doi":"10.1159/000468620","DOIUrl":"https://doi.org/10.1159/000468620","url":null,"abstract":"<p><p>Cathepsin D (Cath D) overexpression in breast cancer cells is associated with increased risk of metastasis in patients according to several clinical studies. The amino acid sequence of Cath D in two breast cancer cell lines was normal, but glycosylation appears to be different with more acidic isoforms. Transfection of a human cDNA Cath D expression vector increases the metastatic potential of 3Y1-Ad12 embryonic rat tumorigenic cells when intravenously injected into nude mide. The mechanism of Cath-D-induced metastasis seems to require maturation of the proenzyme, mostly in large acidic compartments identified as phagosomes. Cath D is mitogenic in different cell types, and different substrates (growth inhibitors, precursors of growth factors, etc.) are proposed to mediate this activity.</p>","PeriodicalId":11854,"journal":{"name":"Enzyme & protein","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000468620","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19766949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S Ruesch, S Krähenbühl, S Kleinle, S Liechti-Gallati, T Schaffner, B Wermuth, J Weber, U N Wiesmann
{"title":"Combined 3-methylglutaconic and 3-hydroxy-3-methylglutaric aciduria with endocardial fibroelastosis and dilatative cardiomyopathy in male and female siblings with partial deficiency of complex II/III in fibroblasts.","authors":"S Ruesch, S Krähenbühl, S Kleinle, S Liechti-Gallati, T Schaffner, B Wermuth, J Weber, U N Wiesmann","doi":"10.1159/000468642","DOIUrl":"https://doi.org/10.1159/000468642","url":null,"abstract":"<p><p>We report on 2 children, brother and sister, who presented with cardiomyopathy and muscular hypotonia at the age of B months. They both excreted significant amounts of 3-hydroxy-3-methylglutaric acid (3-HMG) and 3-methylglutaconic acid (3-MGC) but no 3-methylglutaric acid (3-MG). Enzyme analysis in fibroblasts revealed normal activities of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) lyase and of 3-methylglutaconyl hydratase and other enzymes of 3-HMG metabolism. Loading tests with leucine did not affect the excretion of 3-HMG and 3-MGC. The girl died as a result of her cardiomyopathy, while the boy recovered and was treated with cardiac supportive therapy. He showed a steady improvement during his clinical course with biochemical normalization of the urinary excretion of 3-HMG, concomitant with marked improvement in the hypertrophic cardiomyopathy. In cultured fibroblasts from both patients a reduced activity of complex II/III of the respiratory chain was measured which may be the cause of this new type of 3-HMG uria. Analysis of mitochondrial DNA heart muscle, liver and fibroblast culture of the patient did not reveal any major mitochondrial DNA rearrangements (deletion, duplication) or any point mutation that had been described in association with mitochondrial cardiomyopathy.</p>","PeriodicalId":11854,"journal":{"name":"Enzyme & protein","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000468642","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20196923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Proteases associated with invadopodia, and their role in degradation of extracellular matrix.","authors":"W T Chen","doi":"10.1159/000468616","DOIUrl":"https://doi.org/10.1159/000468616","url":null,"abstract":"<p><p>Metastasizing cancer cells invade the extracellular matrix using plasma membrane protrusions (invadopodia) that contact and dissolve the matrix. Evidence suggests that membrane-associated proteases, 170-kD gelatinase (seprase) and Gelatinase A, exert their mechanisms of action on invadopodia. Potential roles that other metallo- and serine-types of membrane proteases, including membrane-type matrix metalloprotease, meprin, dipeptidyl peptidase IV, fibroblast activation protein alpha and guanidinobenzoatase, play in the cell surface proteolysis are also discussed. It is proposed that formation of a structurally and functionally linked protease complex on invadopodia allows the invasion of cancer cells into the extracellular matrix.</p>","PeriodicalId":11854,"journal":{"name":"Enzyme & protein","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000468616","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19766945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M Miyanaga, H Sugimoto, T Komoda, O Nosjean, K Honma, K Nemoto, T Sato
{"title":"A variant alkaline phosphatase detected in a patient with lung cancer.","authors":"M Miyanaga, H Sugimoto, T Komoda, O Nosjean, K Honma, K Nemoto, T Sato","doi":"10.1159/000468641","DOIUrl":"https://doi.org/10.1159/000468641","url":null,"abstract":"<p><p>A variant alkaline phosphatase (ALP), with heat-sensitivity characteristics similar to that of the bone type, was found in the serum of a patient suffering from lung cancer. In disc polyacrylamide gel electrophoretic studies most of this enzyme had migrated to the region corresponding to liver ALP, with the remainder affecting bone ALP. Like kidney ALP, this ALP was markedly inhibited by 0.5 mmol/l L-cysteine. The K(m) of this ALP for p-nitrophenylphosphate was 0.39 mmol/l, similar to that of kidney ALP. The sugar moiety of this enzyme bore greater resemblance to that of kidney ALP than liver or bone ALP. However, immunoprecipitation of this particular ALP was strong with a monoclonal antibody against liver ALP and moderate with an antibody against bone ALP.</p>","PeriodicalId":11854,"journal":{"name":"Enzyme & protein","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000468641","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20196922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mechanisms controlling the transcription of matrix metalloproteinase genes in normal and neoplastic cells.","authors":"H C Crawford, L M Matrisian","doi":"10.1159/000468614","DOIUrl":"https://doi.org/10.1159/000468614","url":null,"abstract":"<p><p>Matrix metalloproteinases (MMPs) are expressed in normal remodeling tissues in a generally tissue-restricted pattern. Transcripts for stromelysin-1 and collagenase are expressed primarily in stromal fibroblasts, whereas transcripts for matrilysin are expressed primarily in glandular epithelial cells. These expression patterns are maintained at carcinoma tumor sites until the late stages of tumor progression at which point many epithelially-derived tumors begin to express stromal fibroblast MMPs. Coincidentally, late stage carcinomas take on other characteristics of stromal fibroblasts, indicating that these tumor cells have \"transdifferentiated', that is, they have begun to exhibit characteristics of cells from a separate developmental lineage. Despite their distinct expression patterns, many of the promoters for MMP genes show the same general arrangement of the nuclear proto-oncoprotein-binding sites, AP-1 and PEA3. However, the specific interaction between these cis-elements and different combinations of Fos, Jun, and Ets proteins which recognize these sites may be important in controlling both the positive and negative regulation involved in the tissue-restricted pattern of MMP expression in normal and neoplastic tissues.</p>","PeriodicalId":11854,"journal":{"name":"Enzyme & protein","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000468614","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19766943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Stromal cell expression of components of matrix-degrading protease systems in human cancer.","authors":"R Hewitt, K Danø","doi":"10.1159/000468623","DOIUrl":"https://doi.org/10.1159/000468623","url":null,"abstract":"<p><p>Components of matrix-degrading protease systems are in human cancer often expressed by tumour-infiltrating stromal cells. The cellular pattern of expression of these molecules appears to be unique for each type of cancer. In several cases there are similarities with patterns observed in nonmalignant remodelling processes in the same tissue. These findings indicate that the stromal cells actively participate in the process of cancer invasion. The implications of this new paradigm for cancer biology and cancer treatment are discussed.</p>","PeriodicalId":11854,"journal":{"name":"Enzyme & protein","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000468623","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19768266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K Aoyagi, S Nagase, C Tomida, K Takemura, K Akiyama, A Koyama
{"title":"Synthesis of guanidinosuccinate from argininosuccinate and reactive oxygen in vitro.","authors":"K Aoyagi, S Nagase, C Tomida, K Takemura, K Akiyama, A Koyama","doi":"10.1159/000468629","DOIUrl":"https://doi.org/10.1159/000468629","url":null,"abstract":"<p><p>Synthesis of guanidinosuccinic acid (GSA), a uremic toxin, has been suggested to relate to the urea concentration and synthetic rate. Among the urea cycle enzymes, inhibition of argininosuccinate (ASA) lyase by urea has been reported. Argininosuccinate which contains a GSA structure is a candidate of a GSA precursor. We found that another uremic toxin, methylguanidine, is formed from creatinine with reactive oxygen species. Therefore, we investigated in vitro whether GSA is formed from ASA with reactive oxygen species. GSA was measured by HPLC by a post-column-labeling method using 9,10-phenathrequinone. When 1 mmol/l ASA was reacted with the hydroxyl radical-generating system for 5 min at pH 7.4, 9 mumol/l GSA was formed. Dimethylsulfoxide, a hydroxyl radical scavenger, markedly inhibited GSA synthesis. The superoxide radical generated by xanthine and xanthine oxidase reaction also formed 1 mumol/l GSA from 1 mumol/l ASA and the GSA formation was inhibited by superoxide dismutase or catalase almost completely. Addition of FeCl2 to the xanthine/xanthine oxidase reaction further increased GSA synthesis. These results indicate that GSA is formed from ASA by reaction with the hydroxyl radical and the superoxide radical.</p>","PeriodicalId":11854,"journal":{"name":"Enzyme & protein","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000468629","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19988182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Micromethod for the fluorimetric determination of plasma N-acetyl-alpha-D-galactosaminidase and study of some of its characteristics.","authors":"W R Den Tandt, S Scharpé","doi":"10.1159/000468637","DOIUrl":"https://doi.org/10.1159/000468637","url":null,"abstract":"<p><p>We have studied some characteristics of N-acetyl-alpha-D-galactosaminidase in human plasma using a sensitive and very simple fluorimetric (single tube incubation/fixation) micromethod. The enzyme has a pH optimum at 4.5, is linear on incubation during at least 6 h, is protected from inactivation at room temperature by acidification, and is stable on freezing (about 85% residual activity after 1 year at -20 degrees C). Enzyme kinetics indicate that the affinity for the substrate is low (K(m) value 7 mmol/l). By studying about 10 possible effectors, no activation was found by detergents. As expected, the colorigenic p-nitrophenyl derivative substrate, N-acetylgalactosamine and galactose are low-affinity inhibitors. A histogram of 108 control samples showed a unimodal distribution pattern with a slight bias to the right. No pseudodeficients were found on analysis of 220 control plasma samples. Patients with alpha-galactosaminidosis had residual activity between 0.7 and 2.1%. In patients with 17 different lysosomal storage diseases, no increase was found except in mucolipidosis II and III. The main advantages of the method are its simplicity sensitivity, short incubation time requirement and economy in substrate consumption. The method can be used either for screening or diagnostic purposes of genetic N-acetyl-alpha-D-galactosaminidase deficiency.</p>","PeriodicalId":11854,"journal":{"name":"Enzyme & protein","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000468637","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20195754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Kinetic studies of the effects of K+, Na+ and Li+ on the catalytic activity of human erythrocyte pyridoxal kinase.","authors":"P Lainé-Cessac, P Allain","doi":"10.1159/000468639","DOIUrl":"https://doi.org/10.1159/000468639","url":null,"abstract":"<p><p>Kinetic studies were conducted to examine the effects of K+, Na+ and Li+ on human erythrocyte pyridoxal kinase (PK) activity. A dialyzed hemolysate served as the PK source. The substrates used were pyridoxal (PL) and ATP. Determination of the enzymatic activity was based on HPLC separation and fluorimetric detection of PL and pyridoxal 5'-phosphate as semicarbazone derivatives. In comparison to the poor activity of PK assayed without monovalent cation, all tested cations are activators. Among them, K+ is the most effective, improving both PK affinity for the substrates and maximal velocity. Na+ increases maximal velocity and PK affinity for ATP but decreases it for PL. Li+ is a poor activator which seems to modify the enzymatic mechanism from a random to an ordered sequential pattern with ATP bound before PL. Results suggest that K+ and Na+ bind to PK on the same site while Li+ binds on another site. This hypothesis and the mechanism of monovalent cation-PK interaction are compared to other well-known K(+)-activated enzymes.</p>","PeriodicalId":11854,"journal":{"name":"Enzyme & protein","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000468639","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20196920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}