Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Human polymorphonuclear leucocyte elastase and cathepsin G were incubated with preparations of isolated human glomerular basement membrane at neutral pH and 37 degrees C. 2. The ability of these enzymes to degrade glomerular basement membrane was followed by the release of hydroxyproline. Both proteinases released considerable amounts of hydroxyproline. 3. By using Sephadex G-100 it was shown that the solubilized basement membrane fragments appeared as a single peak and had a molecular weight of over 100 000. These proteins after reduction were analysed by sodium dodecyl sulphate-gel electrophoresis to examine their subunit pattern and determine their molecular size. 4. The released basement membrane proteins gave at least four precipitin lines with a rabbit anti-(glomerular basement membrane) antiserum. 5. These results support the concept that polymorphonuclear leucocyte neutral proteinases play an important role in the pathogenesis of glomerulonephritis. 6. At acid pH values cathepsin B also released hydroxyproline from human glomerular basement membrane but the lysosomal carboxyl proteinase, cathepsin D, had no action.
Clin Sci Mol Med 1978 Mar
PMID:The degradation of human glomerular basement membrane with purified lysosomal proteinases: evidence for the pathogenic role of the polymorphonuclear leucocyte in glomerulonephritis. 63 Aug

A wheat gene (A121) encoding a protein with sequence similarity to mammalian cathepsin B is regulated by gibberellic acid (GA) in aleurone layers of germinating grains. To analyse the mechanism of A121 regulation, its promoter was fused to the beta-glucuronidase reporter gene (GUS) and introduced by micro-projectile bombardment into aleurone layers of oat. With 2.3 kb of promoter sequence, the GUS expression was enhanced by GA treatment. This effect was reversed by abscisic acid (ABA). This result showed for A121, like the alpha-amylase genes, that the regulation by GA and ABA was at the level of transcription. The GA responsiveness of the promoter was retained with as little as 276 bp of promoter sequence. Sequence comparison with a GA responsive promoter of an alpha-amylase gene identified the conserved element GCAACGGCAACGATGG which is required intact for full expression of both promoters. However, there was no identifiable similarity in the cathepsin-like promoter with the GA-responsive element of alpha-amylase promoters with the consensus sequence TAACAAA, suggesting that GA affects more than one mechanism of transcriptional control.
Plant Mol Biol 1992 Dec
PMID:Analysis of the gibberellin-responsive promoter of a cathepsin B-like gene from wheat. 146 24

Recombinant phage containing putative Ostertagia ostertagi cysteine protease genes have been isolated from a lambda EMBL-3:genomic DNA library using a Haemonchus contortus cathepsin B-like cysteine protease cDNA as hybridization probe. Restriction enzyme maps of the phages suggest that they identify at least 3 genes, 2 of which appear to be linked in tandem. The complete nucleotide sequence of one gene, CP-1, was determined. The CP-1 gene appears to be organized into 12 exons than span 4.5 kb of DNA. The number and sizes of the exons are essentially identical to those in the H. contortus AC-2 cysteine protease gene. Partial nucleotide sequences obtained for a second O. ostertagi gene, CP-3, revealed a similar organization for exons 8-12 in this gene. Like other cathepsin B-like cysteine proteases, CP-1 appears to be synthesized initially as a preproprotein that is proteolytically processed to its mature form. The amino acid identity between the presumptive CP-1 and CP-3 proteins is 66%, which is similar to the level of homology between the presumed mature protein regions of CP-1 and AC-2. Amino acid identity between CP-1 and AC-2 is greatest in the mature protein region and lowest in the signal sequence and propeptide regions. The CP-3 protein appears to be most closely related to the H. contortus AC-5 protein. CP-1 and CP-3 display significantly greater homology to H. contortus cysteine proteases than they do to human cathepsin B or the Sm31 cysteine protease of Schistosoma mansoni (about 40% identity with each).
Mol Biochem Parasitol 1992 Nov
PMID:Isolation of putative cysteine protease genes of Ostertagia ostertagi. 147

Three new members of a developmentally regulated cysteine protease gene family of the parasitic nematode Haemonchus contortus have been isolated and characterized. One of the new genes, AC-3, was found to be linked in tandem to the previously characterized AC-2 gene. Nucleotide sequence analyses revealed that the first 90 amino acids of AC-3 are organized into four exons, similar to the situation in AC-2. A cDNA that appears to be a near full-length copy of the AC-3 gene was isolated using the polymerase chain reaction (PCR) technique to amplify cDNAs from adult worm poly(A)+ mRNAs. In addition to AC-3, a distinct cysteine protease cDNA, AC-4, was amplified by the same oligonucleotide primers. cDNAs encoding a fifth cysteine protease, AC-5, were isolated from an adult worm cDNA expression library using specific rabbit antisera and by PCR. Comparison of the predicted amino acid sequences of AC-3, AC-4 and AC-5 reveal that they share 64-77% identity with one another and with the previously reported AC-1 and AC-2 sequences. The amino acids surrounding the active site cysteine are highly conserved, as are the positions of other cysteine residues in the mature protein sequences. The H. contortus proteases are more similar to one another than they are to human cathepsin B (38-44% amino acid identity) or to the Sm31 cysteine protease of Schistosoma mansoni (36-40% identity). Our studies indicate that H. contortus adult worms express mRNAs for several distinct cysteine proteases. The significant primary sequence differences between the proteases suggest that they differ in their substrate specificities and precise physiological functions.
Mol Biochem Parasitol 1992 Apr
PMID:Cloning and sequence comparisons of four distinct cysteine proteases expressed by Haemonchus contortus adult worms. 157 79

A Caenorhabditis elegans cysteine protease gene fragment, amplified by PCR using conserved eukaryotic protease gene sequences as primers, was used as a probe to isolate cDNA and genomic clones. The genomic clone, which had a coding sequence of 987 bp interrupted by 2 small introns, was physically mapped to the middle of linkage group V. The predicted amino acid sequence of the mature C. elegans cysteine protease was homologous to those of other eukaryotic cysteine proteases, particularly to that of the nematode parasite Haemonchus contortus (50%) and to the cathepsin B-like hemoglobinase of the trematode parasite Schistosoma mansoni (54%). The pro region of the C. elegans protease was homologous only to that of the H. contortus enzyme, implying a similar mechanism of protease activation. The C. elegans cysteine protease gene was temporally regulated: abundant 1.1-kb transcripts were detected in larvae and adults, but not in embryos. Transcription also was spatially regulated, occurring only in the intestine. Like the vitellogenin genes, which also are transcribed exclusively in the intestine, the 5' end of the C. elegans cysteine protease gene had at least one copy of each of 2 heptameric sequences which may be transcriptional regulatory elements governing gut-specific expression.
Mol Biochem Parasitol 1992 Apr
PMID:Gut-specific and developmental expression of a Caenorhabditis elegans cysteine protease gene. 157 82

We previously found that the T24 Ha-ras oncogene induces metastatic ability in NIH 3T3 cells and that this change depends on expression of the ras oncogene. As part of our studies on mechanisms by which ras may induce metastasis, we investigated expression and activity of two cysteine proteinases, cathepsin L (major excreted protein) and cathepsin B, as well as cysteine proteinase inhibitor activity, in ras-transformed NIH 3T3 cells. In a series of cel lines that expressed differing amounts of ras, we found a good correlation between levels of ras expression and cathepsin L expression (r = 0.80). There was also a good correlation between secreted procathepsin L protein levels and experimental metastatic ability (r = 0.88). We found a similar but less strong association between cathepsin B levels and metastatic ability in these cells (r = 0.76 and r = 0.72 for 2.2-kb and 4.1-kb transcripts, respectively). Functional cathepsin L plus B activity (both secreted and cell-associated) was found to be higher in ras-transformed cells and was dependent on cell confluency in culture. Coupled with increased expression and activity of cysteine proteinases, ras-transformed NIH 3T3 cells showed reduced cysteine proteinase inhibitor activity. We conclude that the balance between expression of cysteine proteinases and their inhibitors may be coregulated by ras expression. Our results suggest that ras-induced increases in production of degradative enzymes such as cathepsins L and B, along with decreased activities of their inhibitors, may contribute to the increased malignant properties of ras-transformed NIH 3T3 cells.
Mol Carcinog 1992
PMID:Increased expression of cathepsins L and B and decreased activity of their inhibitors in metastatic, ras-transformed NIH 3T3 cells. 158 50

Six granular cell tumors (GCT) of the neurohypophysis were studied by immunohistochemical techniques. They were all labeled by peanut lectin (Arachis hypogaea) and three showed reactivity for S-100 protein. Unlike extracranial GCT, neuron specific enolase (NSE), myelin basic protein (MBP) and vimentin were not detected in the tumor cells. Glial fibrillary acidic protein (GFAP), keratin and desmin were also not observed. On the other hand, some showed reactivity for alpha-1-antitrypsin (AAT), alpha-1-antichymotrypsin (AAC) and cathepsin B. These results suggest that neurohypophysial GCT have some features different from extracranial GCT and that they may not be derived from Schwann cells.
Virchows Arch B Cell Pathol Incl Mol Pathol 1991
PMID:Immunohistochemical study of granular cell tumors of the neurohypophysis. 168 58

Administration of the antimalaria drug chloroquine increased the number of autophagic vacuoles (AVs) in the rat pancreas. Ultrastructural analysis showed that AVs contained segregated organelles such as mitochondria, zymogen granules, peroxisomes and small portions of cytoplasm. The maximum number of AVs was observed after 3 h of chloroquine treatment. The effect lasted for 12 h and almost disappeared after 16 h. The increase in AVs caused by chloroquine made it possible to isolate them in a discontinuous Metrizamide gradient with high purity. The proteolytic capacity of the AVs isolated after different chloroquine exposure times was measured after prelabeling pancreatic proteins with an injection of L-(1-14C)leucine 16 h before sacrifice. Protein degradation in isolated AVs increased during the first 6 h of chloroquine exposure and then returned to control values 16 h after the administration. In addition, the activities of two lysosomal enzymes, acid phosphatase and cathepsin B, increased in the AV-fractions following chloroquine treatment. It is concluded that the augmented proteolysis in the isolated AVs is due to a combination of increased substrate content and increased proteolytic lysosomal enzyme activities.
Virchows Arch B Cell Pathol Incl Mol Pathol 1991
PMID:Proteolysis in isolated autophagic vacuoles from the rat pancreas. Effects of chloroquine administration. 168 22

Histochemical localization of cathepsin B in alveolar macrophages (AM) that separated into four different density fractions (I, II, III and IV) by discontinuous Percoll gradient centrifugation was demonstrated in fluorescence microscope using CBZ-Arg-Arg-4-methoxy-2- naphthylamide as a substrate and 5-nitrosalicylaldehyde as a coupling reagent. The least dense AM (fraction I) was found numerous bright yellow fluorescing particles with high intensity in small granules distributed throughout the cytoplasm when compared to the most dense cells (fraction IV). The different localization of cathepsin B activity in the fractionated cells suggested differentiation of lysosomal system and existence of maturational (or aging) sequence in rat AM.
Cell Mol Biol 1991
PMID:Fluorescence demonstration of cathepsin B activity in fractionated alveolar macrophages. 183 40

The metabolic changes in the connective tissue glycosaminoglycans were studied in tissues of adjuvant induced arthritic rats. Arthritic process was induced in rats with the inoculation of Freund's adjuvant containing heat killed Mycobacterium tuberculosis in paraffin oil. The connective tissue glycosaminoglycans were fractionated into sulfated and non-sulfated glycosaminoglycans by chemical and enzymatic methods. The biosynthesis of sulfated glycosaminoglycans was examined using radioactive labeled (35S)-sulfate incorporation measurements into the sulfated glycosaminoglycans in tissues such as liver, kidney, spleen and skin of arthritic rats. The catabolism of glycosaminoglycans was studied by measuring the activity of various connective tissue degrading lysosomal glycohydrolases in tissues of experimental animals. In addition, the changes in the contents of total glycosaminoglycans, mono-sulfated, highly-sulfated and non-sulfated glycosaminoglycans were quantitatively assessed in diseased tissues. Alterations in the metabolism of connective tissue glycosaminoglycans were demonstrated in tissues of arthritic rats. The uptake of (35S)-sulfate into the tissue was found to be increased in liver, kidney and spleen, while that of skin decreased during the process of arthritis. The total glycosaminoglycan content was significantly elevated in diseased tissues compared to normal. Similarly, mono-sulfated, highly-sulfated and non-sulfated glycosaminoglycans were found to be increased in arthritic tissues. In addition, the activity of various connective tissue degrading lysosomal glycohydrolases such as beta-glucuronidase, beta-N-acetylglucosaminidase, cathepsin B, cathepsin L and collagenolytic cathepsin was increased in tissues of arthritic rat. The results presented in this communication indicate that the characteristic alterations were induced in the metabolism of glycosaminoglycans by the dynamic process of adjuvant arthritis.
Mol Cell Biochem 1991 Aug 14
PMID:Metabolism of glycosaminoglycans in tissues of adjuvant arthritic rat. 192 17


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