Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01034 (cystatin C)
 3,397 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cystatin C, a 13 kDa-protein, is produced by most nucleated cells and is catabolized by the renal tubular cells after passing the glomerular filter. It belongs to the family 2 of the cystatin superfamily of proteins. The function of cystatin C is to regulate the activity of cysteine proteinases and cystatin C seems to be the main cysteine proteinase inhibitor of most investigated human biological fluids. Its normal level in plasma is 0.8-2.5 mg/l, in cerebrospinal fluid 4-14 mg/l and in urine 0.03-0.3 mg/l. The production rate of cystatin C is remarkably constant and its plasma concentration can therefore be used as a reliable measure of the glomerular filtration rate (GFR). Indeed, the cystatin C plasma concentration is more closely correlated to the GFR than the plasma levels of creatinine and all other investigated low molecular weight proteins, including beta 2-microglobulin and retinol binding protein. Protein HC, alias alpha 1-microglobulin, is produced by the liver as a 27 kDa-glycoprotein. It belongs to the lipocalin superfamily of hydrophobic ligand binding proteins and more than 50% of the normal plasma amount of protein HC is present as a high molecular weight HC-IgA complex carrying antibody activity. The plasma concentration of free protein HC is, in contrast to that of HC-IgA, mainly determined by the GFR. The normal values for the plasma concentrations of HC-IgA and free protein HC are 36-620 mg/l and 14-26 mg/l, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diagnostic value of analysis of cystatin C and protein HC in biological fluids. 128 35

The effect of human recombinant cystatin C, a cysteine proteinase inhibitor, on bone resorption in vitro was evaluated. Bone resorption was assessed by analyzing the release of 45Ca and 3H from mouse calvarial bones prelabeled in vivo by injections with 45Ca or [3H]proline, respectively. In 24 h cultures, cystatin C (50 micrograms/ml) significantly inhibited the release of 45Ca and 3H stimulated by parathyroid hormone (PTH, 15 nmol/liter) or parathyroid hormone-related peptide of malignancy (PTHrP, 15 nmol/liter). The degree of inhibition caused by cystatin C in these 24 h cultures was similar to that caused by calcitonin (30 ng/ml). The inhibitory effect of cystatin C on 45Ca release induced by PTH was sustained in 96 h cultures, whereas the initial inhibition caused by calcitonin was transient. Cystatin C, 10-100 micrograms/ml, caused a dose-dependent inhibition of PTH (15 nmol/liter), and PTHrP (15 nmol/liter) stimulated 45Ca release. Addition of 50 micrograms/ml of cystatin C to mouse bone cultures inhibited the release of 45Ca induced by PTH and PTHrP at a wide range of submaximal and maximal concentrations of hormones (0.01-10 nmol/liter). No effect of cystatin C on 45Ca release in dead bones could be observed, nor did the inhibitor decrease the release of calcium in control bones. The inhibition by cystatin C on PTH-induced mineral mobilization was reversible. Cystatin C (1-100 micrograms/ml) did not affect protein synthesis or mitotic activities in mouse calvarial bones as assessed by the incorporation of [3H]proline and [3H]thymidine, respectively. These data show that cystatin C is a potent inhibitor of mineral mobilization and matrix degradation in cultured bones stimulated to resorb by PTH and PTHrP and that this effect is not due to general cytotoxicity.
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PMID:Human cystatin C, a cysteine proteinase inhibitor, inhibits bone resorption in vitro stimulated by parathyroid hormone and parathyroid hormone-related peptide of malignancy. 131 5

The Sertoli cells of the rat testis produce cystatin C, a cysteine proteinase inhibitor. Primary culture of Sertoli cells secreted both unglycosylated and glycosylated forms of rat cystatin C. Despite the low concentration of cystatin C in rete testis fluid, equilibrium dissociation constants (Ki) for the interaction between cystatin C and lysosomal cathepsins indicate that this molecule could be involved in the local regulation of testicular cysteine proteinase activity which may be necessary for spermatogenesis and spermiogenesis.
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PMID:Production of the cysteine proteinase inhibitor cystatin C by rat Sertoli cells. 156 13

A solid-phase enzyme-linked immunosorbent assay (ELISA) for determining human serum cystatin C is described. In 50 normal samples, cystatin C concentration was 1247 +/- 224 micrograms/L (mean +/- SD) which is in agreement with previously reported levels. Serum levels of cystatin C and beta 2-microglobulin (beta 2-M) were investigated in a time-course study during the development of human immunodeficiency virus (HIV) infection. We found a persistent and uniform increase in the beta 2-M concentration (2762 +/- 1239 micrograms/L). In contrast to beta 2-M, on the basis of cystatin C levels, we found two distinct populations, one of which demonstrated an increased concentration (1620 +/- 618 micrograms/L). Interestingly a second group (21% of patients) exhibited an initial significant decrease in cystatin C concentration with a mean value of 377 (range 55-850) micrograms/L, followed by an increase. The biphasic pattern of cystatin C serum, a major cysteine proteinase inhibitor, during the course of HIV infection suggests a possible role for these proteinases (or proteinase inhibitors) in the development of this syndrome.
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PMID:Cystatin C levels in sera of patients with human immunodeficiency virus infection. A new avidin-biotin ELISA assay for its measurement. 156 12

The TT cell line of human medullary thyroid carcinoma, that retains some of the differentiated functions of thyroid C cells including the synthesis and secretion of calcitonin, was found to contain and release into the culture medium cysteine proteinase inhibitor(s), cystatin(s). The major inhibitor, which is similar to, if not identical with, cystatin C, is constitutively released, or secreted, by TT cells. The rate of secretion of cystatin, quantified by titration of inhibition of papain, was stimulated by dibutyryladenosine 3':5'-cyclic monophosphate, forskolin, the calcium ionophore A 23187, and by the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). Neither forskolin nor TPA had, however, an effect on the level of the inhibitor in TT cells. Treatment with n-butyrate strongly inhibited the proliferation of TT cells, and led, in 4 to 7 days, to a doubling of the intracellular concentration of cystatins. Northern blot hybridizations to a 32P-labeled riboprobe complementary to human cystatin C cDNA indicated that cAMP, forskolin, and TPA had no effect on the steady-state levels of cystatin C mRNA. These data indicate that release of cystatin(s) from TT cells is regulated by cAMP-calcium-protein kinase C mechanisms that appear to be similar to those that regulate the secretion of calcitonin from these cells. However, in contrast to the calcitonin gene, the expression of the cystatin C gene in these cells is not regulated by cAMP or TPA. By a combination of acetone fractionation, affinity chromatography on Cm-papain-Sepharose, and gel exclusion chromatography a protein of approximately 14 kilodaltons was isolated from TT cells that reacted with antibodies against human cystatin C, and strongly inhibited papain. Cystain secreted by TT cells also had a molecular weight of 14 kilodaltons, and reacted with anti-human cystatin C antibodies. The physiologic and pathologic roles of cystatins in different cell types remain to be established. The TT cells provide a suitable cell type to study the regulation of the expression of the cystatin gene and the mechanism of cystatin release.
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PMID:Cysteine proteinase inhibitor in cultured human medullary thyroid carcinoma cells. 160 39

The effect of four human serine proteinases on the human cysteine proteinase inhibitor, cystatin C, has been studied in vitro. Neutrophil elastase in catalytic amounts was observed to rapidly cleave cystatin C at neutral pH, thereby giving rise to a modified form of the inhibitor lacking the N-terminal Ser1-Val10 decapeptide. The two other leukocyte serine proteinases, cathepsin G and neutrophil proteinase 4, did not catalytically hydrolyse cystatin C bonds. Neither had the seminal plasma serine proteinase, prostate-specific antigen, any effect on cystatin C. The physiological implications of neutrophil elastase catalysed modification of cystatin C are discussed, and recent findings indicating that this reaction also occurs in vivo are reviewed.
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PMID:Regulation of cystatin C activity by serine proteinases. 180 27

Recent work has demonstrated that a tripeptide derivative mimicking the active proteinase-binding site of cystatin C, a human cysteine proteinase inhibitor, can block growth of group A streptococci and replication of herpes simplex virus (HSV). In the case of HSV, intact cystatin C was also found to inhibit replication of the virus. Many streptococcal strains and HSV-infected cells produce immunoglobulin (Ig)-binding proteins, and a possible connection between such proteins and proteolytic activity was indicated by the finding that bacterial Ig-binding proteins also show affinity for proteinase inhibitors. The significance of these various observations is not clear, but available data suggest that proteinases play a role in vital microbial functions (e.g. viral replication) and may be utilized as targets for antimicrobial agents. The results discussed here also indicate that peptide derivatives based on the structure of proteinase inhibitors occurring in nature could be used as such agents.
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PMID:Proteinase inhibition, immunoglobulin-binding proteins and a novel antimicrobial principle. 196 37

The gene for the human cysteine proteinase inhibitor stefin A (STF1), alias cystatin A, has been mapped to chromosome 3, using the polymerase chain reaction to specifically amplify the human stefin A sequence in human-hamster hybrid DNA. STF1 is further sublocalized to regions between centromere and 3q21 using a deletion mapping panel for this chromosome. This assignment shows that stefin A is not syntenic with cystatin C which has been localized to chromosome 20.
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PMID:Mapping of the gene for human cysteine proteinase inhibitor stefin A, STF1, to chromosome 3cen-q21. 200 63

Cystatin C is a human cysteine proteinase inhibitor present in extracellular fluids. Cystatin C and a tripeptide derivative (Z-LVG-CHN2) that mimics its proteinase-binding center, were tested for possible antiviral activity against herpes simplex virus type 1 (HSV) and poliovirus type 1. Both recombinant cystatin C and Z-LVG-CHN2 displayed strong inhibitory effects on HSV replication, whereas no significant effect on poliovirus replication was seen. The molar concentration of cystatin C that gave total inhibition of HSV replication was lower than that of either Z-LVG-CHN2 or of acyclovir, the drug currently most used against HSV infections. These results suggest that cysteine proteinase inhibitors might play a physiological role as inhibitors of viral replication and that such proteinase inhibitors, or peptide derivatives that mimic their proteinase-binding centers, might be used as antiviral agents.
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PMID:Cystatin C, a human proteinase inhibitor, blocks replication of herpes simplex virus. 215 54

Cystatin C, a cysteine proteinase inhibitor has recently been suggested to be a potent regulator of inflammatory processes and may act in defense against viral and bacterial infections. Two common forms of the protein were purified from the urine of a patient having received a renal transplant. The slow form of cystatin C possessed the N-terminal tetrapeptide Lys Pro Pro Arg, which was cleaved in the fast form. This peptide sequence, called postin, was synthesized. The three molecules, slow and fast forms of cystatin and the synthetic peptide, were tested for their effects on the migration activity of human polymorphonuclear neutrophils (PMNs). The slow form was found to display both chemotactic and chemokinetic activities, while the fast form and postin were only chemokinetic. Nevertheless, all the substances could induce a "motile" morphology. In addition, the two forms of cystatin C were powerful inhibitors of PMN chemotaxis induced by complement-derived chemotactic factors. This suggests that cystatin C in its two different cleaved forms and the N-terminal tetrapeptide can modulate PMN locomotion. Cysteine proteases may therefore play a role in neutrophil migration activity.
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PMID:Neutrophil chemotactic activity is modulated by human cystatin C, an inhibitor of cysteine proteases. 236 32


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