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)

Cytosoluble 100,000 X g extracts from Plasmodium berghei or Plasmodium falciparum infected red blood cells were shown to hydrolyze erythrocyte spectrin. By Fast Protein Liquid Chromatography (FPLC), these enzymes were purified and exhibited a pI of 4.5 and Mr of 37,000 using SDS-PAGE under reducing conditions. An immunochemical enzyme assay using anti-spectrin antibodies was developed. The optimal activity using spectrin as substrate was at pH 5.0, and the enzymes were strongly inhibited by HgCl2, ZnCl2, chymostatin, leupeptin and aprotinin, and moderately by pepstatin. These properties of the Pf37 and Pb37 proteases differ from the Plasmodium lophurae and P. falciparum 'cathepsin D-like' enzymes and from the serine or cysteine neutral proteases previously described in P. falciparum and P. berghei infected red blood cells. While the Pf37 and Pb37 enzymes cleaved spectrin preferentially, degradation of band 4.1 was also observed with high concentration of enzyme. The parasite origin of the Pf37 protease was clearly demonstrated, since purified radiolabeled enzyme was active on spectrin. A high-molecular-weight polymer (greater than 240 kDa) was often observed on incubating purified spectrin and Pf37 protease. The breakdown of erythrocyte cytoskeletal components could be of interest in the release of merozoites from segmented schizonts or during the process of invasion of erythrocytes by merozoites.
Mol Biochem Parasitol 1990 Jan 15
PMID:Purification and characterization of 37-kilodalton proteases from Plasmodium falciparum and Plasmodium berghei which cleave erythrocyte cytoskeletal components. 218 48

The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the growth of estrogen-responsive MCF-7 human breast cancer cells in the presence of 17 beta-estradiol was determined. After treatment with 17 beta-estradiol (1 nM), TCDD (10 nM) and 17 beta-estradiol (1 nM) plus TCDD (10 nM) the cells were monitored daily for cell growth and DNA content for 7 days. The results showed that TCDD inhibited cell proliferation and DNA content of untreated cells and inhibited the 17 beta-estradiol-stimulated cell proliferation and increase in cellular DNA content. In contrast, TCDD did not effect the growth of estrogen non-responsive MDA-MB-231 human breast cancer cells. TCDD (0.1-10 nM) also caused a concentration-dependent decrease in the 17 beta-estradiol-induced proliferation in MCF-7 cells. The effects of TCDD on the 17 beta-estradiol-induced secretion of the 52-kDa protein (i.e. procathepsin D), the 34-kDa (cathepsin D) and 160-kDa proteins were also determined in the MCF-7 and MDA-MB-231 human breast cancer cell lines. The levels of the proteins were determined by autoradiographic analysis of the incorporation of [35S]methionine into the secreted proteins which were separated by denaturing sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Treatment of MCF-7 cells with 17 beta-estradiol (1 nM), TCDD (10 and 100 nM) and 17 beta-estradiol (1 nM) plus TCDD (10 nM) resulted in levels of the 52-kDa protein which were 497, 63.6, 98.1 and 66.3%, respectively, of the corresponding levels observed in control (untreated) cells. Using the same concentrations, the levels of the 34-kDa protein secreted into the media were 372, 42.3, 64.0 and 43.8% of control values, respectively, and the corresponding levels of the 160-kDa protein were 381, 52.9, 71.2 and 76.6% of the control values, respectively. In contrast, treatment of MDA-MB-231 cells with 17 beta-estradiol (1 nM), TCDD (10 and 100 nM) and 17 beta-estradiol (1 nM) plus TCDD (10 nM) resulted in a 31-39% reduction in the secretion of the 52-kDa protein however these effects were not statistically different from the control values. In addition, the treatments did not cause any significant effects on the secretion of the 34- and 160-kDa proteins by MDA-MB-231 cells. These results clearly confirm and extend the range of antiestrogenic effects caused by TCDD in estrogen-responsive MCF-7 cells and indicate that the MDA-MB-231 cells are not responsive to the antiestrogenic effects of TCDD.
J Steroid Biochem Mol Biol 1990 Dec 10
PMID:Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on cell growth and the secretion of the estrogen-induced 34-, 52- and 160-kDa proteins in human breast cancer cells. 227 56

We investigated the effect of exogenous oxygen free radicals and various pH on the release of lysosomal hydrolases from dog myocardial lysosomes. A lysosomal enriched fraction from the homogenate of dog heart was prepared, using differential centrifugation technique. Exogenous oxygen free radicals were generated using xanthine-xanthine oxidase system. The release of lysosomal hydrolases was measured from the lysosomal enriched fraction. There was about 3-fold increase in the release of cathepsin D and beta-N-acetylglucosaminidase activities in the preparations treated with xanthine-xanthine oxidase as compared to those without such treatment. The presence of superoxide dismutase, an oxygen free radical scavenger, prevented the release of cathepsin D and beta-N-acetylglucosaminidase from the lysosomes. Sonication and lubrol treatments, which are known to cause membrane disruption, also induced the release of these enzymes from lysosomal enriched fraction. However, this release was not prevented by superoxide dismutase. The changes in pH (4.5, 5.5, 6.0, 6.5, 7.4, 8.0) alone did not cause any increase in the enzyme release. The presence of oxygen free radicals at each pH resulted in a similar increase in the release of cathepsin D and beta-N-acetylglucosaminidase. These studies suggest that oxygen free radicals and not the alterations in pH are primarily responsible for the release of lysosomal hydrolases. Oxygen free radicals, in addition to their direct myocardial damaging effect, may also be responsible for the cardiac damage through the release of lysosomal enzymes.
J Mol Cell Cardiol 1989 Nov
PMID:Role of oxygen free radicals and pH on the release of cardiac lysosomal enzymes. 260 45

The precursor of cathepsin D, a lysosomal acidic protease, is secreted by human breast cancer cells, where its synthesis is specifically induced by estrogens and growth factors. In this study, we investigated the hormonal regulation of cathepsin D and its mRNA in uterine cells. In the Ishikawa endometrial cancer cell line, epidermal growth factor (EGF) increased the level of cathepsin D and its mRNA 2- to 3-fold. Although expression of the transiently transfected estrogen-responsive recombinant (Vit. tk. CAT) and the endogenous progesterone receptor was markedly increased by estradiol in Ishikawa cells, estradiol did not alter the level of cathepsin D or its mRNA. The progestin R5020 induced the expression of the LTR sp65 CAT, which contains the progesterone-responsive element of the MMTV but it too was without effect on cathepsin D. By contrast, the expression of cathepsin D gene, in normal rat uterus, was increased by R5020 but not by estradiol. We conclude that cathepsin D gene expression is regulated differently by sex steroid hormones in endometrial and breast cancer cell lines, whereas it is similarly induced by EGF in these cells.
Mol Cell Endocrinol 1989 Oct
PMID:Differential regulation of cathepsin D by sex steroids in mammary cancer and uterine cells. 261 33

A cDNA clone containing the entire coding region for bovine pre-alpha-lactalbumin (LA) together with 27 base pairs of 5'-noncoding and 268 base pairs of 3'-noncoding sequences was isolated from a bovine mammary cDNA plasmid library in the Okayama-Berg vector system using a synthetic oligonucleotide probe and sequenced. The coding segment for mature LA was subcloned into the T7 expression system of Studier and co-workers (Studier, F.W., and Moffatt, B.A. (1986) J. Mol. Biol. 189, 113-130; Rosenberg, A.H., Lade, B.N., Chui, D.S., Lin, S.W., Dunn, J.J., and Studier, F.W. (1987) Gene (Amst.) 56, 125-135) and expressed as a 21-kDa fusion protein that consisted of the mature bovine LA sequence connected to the NH2-terminal 50 residues of human cathepsin D by a linker sequence containing protease cleavage sites. This fusion protein was expressed in an insoluble form and accumulated to about 50% of the total bacterial protein within 3 h after induction of T7 RNA polymerase synthesis. The protein was solubilized, purified by gel filtration, and converted to an active form by treatment with mixtures of reduced and oxidized glutathione in the presence of Ca2+. The maximum specific activity of the fusion protein was about 25% of that of native LA, suggesting that the attachment of an NH2-terminal extension sterically hinders but does not prevent the interaction with galactosyltransferase. The extension also does not block the binding of the regulatory Ca2+ ion that is required for folding from the reduced denatured state. Trypsin cleaved the folded fusion protein specifically at a Lys-Glu bond at the junction with the mature LA sequence to give a product indistinguishable in structure and activity from native LA.
 ...
PMID:Recombinant bovine alpha-lactalbumin obtained by limited proteolysis of a fusion protein expressed at high levels in Escherichia coli. 268 74

Eight liver biopsy specimens from five patients with PAS-negative intracisternal hyalin were investigated by immunofluorescence for: (1) immunoglobulins (Ig) G, A, M, D, E; (2) light chains (kappa and lambda); (3) complement components C1q, C4, C3c, C5, C9; (4) C1-inactivator; (5) C3-activator; (6) alpha 1-antitrypsin; (7) alpha 1-antichymotrypsin; (8) plasminogen; (9) fibrinogen; (10) fibrinogen breakdown products D and E; (11) fibronectin; (12) prealbumin; (13) albumin; (14) betalipoprotein; (15) apolipoprotein; (16) alpha 1- and alpha 2-glycoprotein; (17) cholinesterase; (18) ceruloplasmin; (19) haemopexin; (20) myoglobin; (21) placenta lactogen; (22) transferrin; (23) actin; (24) myosin; (25) cathepsin D; and (26) hepatitis B surface and core antigens (HBsAg and HBcAg). The globules reacted significantly with antisera against C3c (three patients), C4 (three patients), C3-activator (one patient) and fibrinogen (two patients). The cause of the protein accumulation is not clear. Serial studies indicate the possibility of a disturbance of protein secretion and an as yet unidentified immune complex disorder.
Virchows Arch B Cell Pathol Incl Mol Pathol 1985
PMID:Immunohistological investigations of PAS-negative globular intracisternal hyalin in human liver biopsy specimens. 285 88

Suramin-induced lysosomal storage disease reproduced in the rat was extended to the mouse with the attempt to characterize enzymatically and morphologically heterogeneous responses of various organs to the drug. Suramin administration strikingly decreased (3-6 days afterward) the activity of beta-glucuronidase in all tissues studied (kidney, liver, heart, and skeletal muscle). The enzymatic responses were small in the activities of beta-N-acetyl-glucosaminidase. The activity of arylsulfatase A decreased to a varying degree in mouse tissues, but in rats the activity increased in liver and skeletal muscle. The activity of cathepsin D increased in rat tissues. Suramin induced morphological changes characteristic to lysosomal storage diseases in kidney and liver but not in heart and skeletal muscle of both mice and rats. Kidney was appreciably more susceptible to suramin than liver. The occurrence of lysosomal accumulations, membranous lamellar inclusions, and granular material were most prominent in tubular cells of kidney and in Kupffer cells of liver. These cells also presented intensive Alcian blue staining. Interestingly, the enzymatic and morphological responses did not correlate with each other, which may reflect differences in the regulation of lysosomal functions in various cell types.
Exp Mol Pathol 1986 Aug
PMID:Morphological and enzymatic heterogeneity of suramin-induced lysosomal storage disease in some tissues of mice and rats. 287 99

AA-amyloidosis was induced in hamsters receiving amyloid-enhancing factor (AEF) by daily subcutaneous injection with either an aged casein solution or casein supplemented with lipopolysaccharide (LPS). Both amyloid inducers gave similar results with respect to amyloid development in spleen, liver and kidneys and to serum amyloid A (SAA) concentrations and plasma cathepsin D activities. AEF was isolated from amyloid-containing tissue by the method described by Hol et al. (1985), and amyloid-enhancing material was also extracted from isolated hamster amyloid fibrils by intensive sonification. This fibril-derived amyloid-enhancing material lacked typical green birefringence after staining with Congo red and appeared as amorphous material on electron microscopy. AEF shortened the pre-amyloid phase for splenic and hepatic amyloid development and also the subsequent interval before renal amyloid deposition. This indicates that endogenous AEF, unlike passively transferred preformed AEF, is not distributed throughout the body and is probably generated at the site of amyloid deposition. Moreover, these results suggest that amyloid deposition in the kidneys, like that in the spleen and liver, involves an AEF-dependent pathway. Thus redistribution of amyloid is probably not an important cause of renal amyloid involvement. In addition to the reduction in the lag phase for splenic and hepatic amyloid deposition, AEF also speeds the changes in SAA concentration and plasma cathepsin D activity. This indicates that AEF accelerates rather than eliminates the pre-amyloid phase.
Virchows Arch B Cell Pathol Incl Mol Pathol 1986
PMID:Amyloid-enhancing factor (AEF) in the pathogenesis of AA-amyloidosis in the hamster. 287 82

In an attempt to clarify the roles of proteases in the developmental mechanisms of hypertensive vascular lesions, changes in activities of aortic elastase, collagenase, and cathepsin D in spontaneously hypertensive rats (SHR) and renal hypertensive rats were biochemically investigated. In SHR, elastase activity initially showed a significant increase, once two-fold higher than that in the control; but the activity tended to decrease earlier than that in the control. In both SHR and normotensive control rats collagenase activities tended to increase with advancing age. The activity in SHR was two-fold higher than that in the control at all ages examined. In both younger SHR and normotensive rats cathepsin D activities proved to be increased with advancing age, while in old rats the activities tended to decrease. The activity in SHR was three- to fivefold higher than that in the control at all ages examined. In renal hypertensive rats, the activities of elastase, collagenase, and cathepsin D increased gradually with increasing blood pressure, at levels significantly higher than those in the control. These findings suggest that the metabolisms of proteins such as elastin and collagen, expressed by these enzyme activities, are accelerated under hypertensive conditions.
Exp Mol Pathol 1986 Apr
PMID:Elastase, collagenase, and cathepsin D activities in the aortas of spontaneously hypertensive and renal hypertensive rats. 300 14

The proteinase A structural gene of Saccharomyces cerevisiae was cloned by using an immunological screening procedure that allows detection of yeast cells which are aberrantly secreting vacuolar proteins (J. H. Rothman, C. P. Hunter, L. A. Valls, and T. H. Stevens, Proc. Natl. Acad. Sci. USA, 83:3248-3252, 1986). A second cloned gene was obtained on a multicopy plasmid by complementation of a pep4-3 mutation. The nucleotide sequences of these two genes were determined independently and were found to be identical. The predicted amino acid sequence of the cloned gene suggests that proteinase A is synthesized as a 405-amino-acid precursor which is proteolytically converted to the 329-amino-acid mature enzyme. Proteinase A shows substantial homology to mammalian aspartyl proteases, such as pepsin, renin, and cathepsin D. The similarities may reflect not only analogous functions but also similar processing and intracellular targeting mechanisms for the two proteins. The cloned proteinase A structural gene, even when it is carried on a single-copy plasmid, complements the deficiency in several vacuolar hydrolase activities that is observed in a pep4 mutant. A strain carrying a deletion in the genomic copy of the gene fails to complement a pep4 mutant of the opposite mating type. Genetic linkage data demonstrate that integrated copies of the cloned proteinase A structural gene map to the PEP4 locus. Thus, the PEP4 gene encodes a vacuolar aspartyl protease, proteinase A, that is required for the in vivo processing of a number of vacuolar zymogens.
Mol Cell Biol 1986 Jul
PMID:PEP4 gene of Saccharomyces cerevisiae encodes proteinase A, a vacuolar enzyme required for processing of vacuolar precursors. 302 36


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