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)

The mutual effects of P. gingivalis and several cystatin species has been investigated. After incubation with P. gingivalis culture supernatant, cystatin S, cystatin C and chicken cystatin were truncated from a 14 kDa protein into a polypeptide of approximately 13 kDa. Amino acid sequence analysis of the truncated cystatin S polypeptide revealed that cystatin S was cleaved after Arg-8. All three types of truncated cystatins fully retained their inhibitory activity toward papain. Cystatin S and chicken cystatin partially inhibited proteolytic activity in the culture supernatant of P. gingivalis. Furthermore, cystatin S and chicken cystatin inhibited the growth of P. gingivalis in culture to 50% at approximately 1 microM.
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PMID:Inhibition of the growth and cysteine proteinase activity of Porphyromonas gingivalis by human salivary cystatin S and chicken cystatin. 899 96

The region of the bacteriophage A2 genome involved in site-specific recombination with the DNA of Lactobacillus spp. has been identified. Two orfs, transcribed from the same strand, have been found immediately upstream of the phage attachment site (attP). The orf adjacent to attP predicts a 385-amino-acid protein that presents significant similarity with site-specific recombinases of the integrase family. The other orf encodes a basic polypeptide of 76 amino acid residues. The junctions of the prophage with the genomes of its hosts have been determined, allowing the identification of the host attachment site (attB), which has a common 19-nucleotide core region with attP. The attB site is located at the 3' end of the transfer RNALeu gene (anticodon CAA). Nonreplicative plasmids containing the A2-specific recombination cassette integrate into different lactobacilli but also into unrelated Gram-positive bacteria such as Lactococcus lactis and even into Escherichia coli. In Lc. lactis, integration occurs in a previously unknown intergenic region, whereas in E. coli, it maps within the rrnD operon, 5' of rrsD gene. Comparison of the integration sites in the different hosts indicates that some flexibility is permitted in the attB sequence, since Lc. lactis and E. coli only share 13 and 11 nucleotides, respectively, with the 19-nucleotide core sequence of the lactobacilli.
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PMID:The site-specific recombination system of the Lactobacillus species bacteriophage A2 integrates in gram-positive and gram-negative bacteria. 977 Apr 32

Cystatin C is a small basic protein with a MW of 13,359 Daltons, consisting of a non-glycosylated polypeptide chain containing 120 amino-acid residues. Cystatin C is produced in all the nucleated cells of the human body and its output rate is constant. The kidney is the main catabolic site of cystatin C, since the protein, by virtue of its low MW and its positive charge at normal pH, is freely filtered by the glomerulus and almost completely reabsorbed, catabolised and broken down in the cells of the proximal convoluted tubule. It is practically entirely filtered via the glomerular membrane, without any significant tubular secretion. The constant production rate of cystatin C in all the tissues, its elimination via the glomerular filter and its non-dependence on many extrinsic factors, including sex, age, diet, inflammation, are potentially ideal conditions for an endogenous biochemical marker of glomerular filtration. A recent method for determining cystatin C, is based on an immune reaction, could increase its clinical application. Not many studies have been conducted to date on cystatin C in children. The cystatin C concentration was higher during the first few days of life (range: 1.64-2.59 mg/L) with a rapid reduction during the first 4 months. Beyond the first year of life, cystatin C concentration became constant, with a reference range of 0.7-1.38 mg/L. On the basis of the data currently available, neonatal serum cystatin C would appear to derive from the newborn itself. In fact no correlations were found between maternal and neonatal serum cystatin C values. Cystatin C determination appears to be at least equivalent to serum creatinine measurement for the assessment of glomerular filtration rate in children. Further extended studies are needed to investigate these aspects more thoroughly in neonates.
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PMID:Cystatin C in paediatric nephrology. Present situation and prospects. 1047 83

Human cystatin C is a cysteine proteinase inhibitor belonging to the cystatin superfamily, which previously has been shown to inhibit bone resorption in bone organ culture. The aminoterminal segment, Arg(8)-Leu(9)-Val(10)-Gly(11) (RLVG), of the single polypeptide chain of cystatin C constitutes an essential part of its inhibitory center. In the present study, the effect of benzyloxycarbonyl-Arg(8)-Leu(9)-Val(10)-Gly(11)-diazomethane (Z-RLVG-CHN(2)) on bone resorption in vitro was compared with the effects of cystatin C and calcitonin. Bone resorption was assessed by the release of (45)Ca and (3)H from mouse calvarial bones prelabeled with [(45)Ca]CaCl(2) and [(3)H]-proline, respectively. Z-RLVG-CHN(2) concentration-dependently inhibited the release of (45)Ca and (3)H in bones stimulated by parathyroid hormone (PTH), with half-maximal inhibition obtained at 1 micromol/L. The inhibitory actions of Z-RLVG-CHN(2) and cystatin C were persistent, whereas action induced initially by calcitonin was lost with time. The inhibition caused by Z-RLVG-CHN(2) and cystatin C on PTH-stimulated (45)Ca release was observed after 6 h, whereas inhibition by calcitonin was seen already after 2 h. In contrast, the inhibitory effects of Z-RLVG-CHN(2) and cystatin C, as well as that of calcitonin, on (3)H release was seen already after 2 h. Z-RLVG-CHN(2), in which the reactive carboxyterminal diazomethane was substituted by nonreactive groups [-OH, -NH(2), or -N(CH(3))(2)], resulted in peptidyl derivatives, which, in contrast to Z-RLVG-CHN(2) and cystatin C, inhibited neither cysteine proteinases nor bone resorption. In contrast to wild-type cystatin C, recombinant human cystatin C with Gly substitutions for residues Arg(8), Leu(9), Val(10), and Trp(106), and with low or nonexistent affinity for cysteine proteinases, did not display any inhibitory effect on bone resorption. These data strongly indicate that Z-RLVG-CHN(2) inhibits bone resorption in vitro by a mechanism that seems primarily to be due to an inhibition of bone matrix degradation via cysteine proteinases. The data also corroborate the hypothesis that cystatin C inhibits bone resorption by virtue of its cysteine proteinase inhibitory capacity.
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PMID:A peptidyl derivative structurally based on the inhibitory center of cystatin C inhibits bone resorption in vitro. 1077 84

The diagnosis of Alzheimer's disease (AD), the most common form of dementia in the general population, usually relies upon the presence of typical clinical features and structural changes on brain magnetic resonance imaging. Over the last decade, a number of biological abnormalities have been reported in the cerebrospinal fluid (CSF) of AD patients, in particular altered levels of the tau protein and the 1-42 fragment of the amyloid precursor protein. These, however, have not yet proved sensitive and specific enough to be included in the diagnostic criteria for AD, leaving plenty of room for the search of novel biomarkers. The present study describes the analysis of CSF polypeptides by a protein-chip array technology called surface enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS). Using this approach, we detected statistically significant quantitative differences (p < 0.05) regarding four overexpressed and one underexpressed polypeptides in the CSF of AD patients as compared to healthy controls. Four of them were further purified by strong anionic exchange chromatography (SAX) and identified by MS analysis as cystatin C, two beta-2-microglobulin isoforms, an unknown 7.7 kDa polypeptide, and a 4.8 kDa VGF polypeptide. The combination of the five polypeptides for the diagnosis of AD allowed to classified six AD patients out of the nine included in this study and all the ten controls, which means in this small cohort that the specificity and sensitivity are 100% and 66%, respectively. This study, based on the protein-chip array technology, demonstrates the presence in the CSF of novel potential biomarkers for AD, which may be used for the diagnosis and perhaps the assessment of the severity and progression of the disease.
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PMID:A panel of cerebrospinal fluid potential biomarkers for the diagnosis of Alzheimer's disease. 1292 74

Low molecular-mass plasma proteins play a key role in health and disease. Cystatin C is an endogenous cysteine proteinase inhibitor belonging to the type 2 cystatin superfamily. The mature, active form of human cystatin C is a single non-glycosylated polypeptide chain consisting of 120 amino acid residues, with a molecular mass of 13,343-13,359 Da, and containing four characteristic disulfide-paired cysteine residues. Human cystatin C is encoded by the CST3 gene, ubiquitously expressed at moderate levels. Cystatin C monomer is present in all human body fluids; it is preferentially abundant in cerebrospinal fluid, seminal plasma, and milk. Cystatin C L68Q variant is an amyloid fibril-forming protein with a high tendency to dimerize. It forms self-aggregates with massive amyloid deposits in the brain arteries of young adults, leading to lethal cerebral hemorrhage. The main catabolic site of cystatin C is the kidney: more than 99% of the protein is cleared from the circulation by glomerular ultrafiltration and tubular reabsorption. The diagnostic value of cystatin C as a marker of kidney dysfunction has been extensively investigated in multiple clinical studies on adults, children, and in the elderly. In almost all the clinical studies, cystatin C demonstrated a better diagnostic accuracy than serum creatinine in discriminating normal from impaired kidney function, but controversial results have been obtained by comparing this protein with other indices of kidney disease, especially serum creatinine-based equations. In this review, we present and discuss most of the available data from the literature, critically reviewing conclusions and suggestions for the use of cystatin C in clinical practice. Despite the multitude of clinical data in the literature, cystatin C has not been widely used, perhaps because of a combination of factors, such as a general diffidence among clinicians, the absence of definitive cut-off values, conflicting results in clinical studies, no clear evidence on when and how to request the test, the poor commutability of results, and no accurate examination of costs and of its routine use in a stat laboratory.
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PMID:Biochemistry and clinical role of human cystatin C. 1560 10

We have cloned a novel gene, Cymg1 (GenBank accession number AY600990), from a mouse testis cDNA library. Cymg1 is located in 2G3 of mouse chromosome 2. The cDNA includes an open reading frame that encodes 141 amino acid residues. The encoded polypeptide has a cysteine protease inhibitor domain found in the family 2 cystatins but lacks critical consensus sites important for cysteine protease inhibition. These characteristics are seen in the proteins of the CRES subfamily of the family 2 cystatins which are expressed specifically in the reproductive tract. CYMG1 protein shows 44% identity with mouse CRES and 30% identity with mouse cystatin C. Northern blot analysis showed that the Cymg1 gene was specifically expressed in adult mouse testis. RT-PCR also showed that Cymg1 was expressed in testis and spermatogonial cells. Cymg1 expression level varied in the different developmental stages of mouse testis, and were coincidental with spermatogenesis and sex maturation. These results indicate that Cymg1 may play important roles in mouse spermatogenesis and sex maturation.
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PMID:Cloning of a novel gene, Cymg1, related to family 2 cystatins and expressed at specific stages of mouse testis development. 1568 28

Oligomerization of human cystatin C (HCC) leads to amyloid deposits in brain arteries, and this process is greatly accelerated with a naturally occurring L68Q variant. The crystal structures of N-truncated and full-length HCC (cubic form) showed dimer formation via three-dimensional (3D) domain swapping, and this observation has led to the suggestion that an analogous domain-swapping mechanism, but propagated in an open-ended fashion, could be the basis of HCC fibril formation. Here we report that full-length HCC, when crystallized in a new, tetragonal form, dimerizes by swapping the same secondary structure elements but with a very different overall structure generated by the flexibility of the hinge linking the moveable elements. The beta-strands of the beta-cores of the two folding units of the present dimer are roughly parallel, while they formed an angle of about 100 degrees in the previous two structures. The dimers pack around a crystallographic dyad by extending their molecular beta-sheets in an intermolecular context. At the other edge of the molecular beta-sheet, side-chain-side-chain hydrogen bonds propagate the beta-structure in the same direction. In consequence, a supramolecular crystal structure is generated, with all the beta-strands of the domain-swapped dimers being perpendicular to one crystallographic direction. This observation is relevant to amyloid aggregation of HCC, as X-ray diffraction studies of amyloid fibrils show them to have ordered, repeating structure, consistent with the so-called cross-beta structure, in which extended polypeptide chains are perpendicular to the fiber axis and form infinite beta-sheets that are parallel to this axis.
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PMID:3D domain-swapped human cystatin C with amyloidlike intermolecular beta-sheets. 1617 Jul 82

Differential proteomic analysis has been performed on the cerebrospinal fluid (CSF) of six healthy and six patients suffering form sporadic Creutzfeldt-Jakob disease (sCJD), age- and sex-matched, after immuno-subtraction of albumin and immunoglobulins. These maps have revealed 28 polypeptide chains differentially modulated in the sCJD samples, of which 10 appeared to be up-regulated, the remaining 18 being down-regulated. Among those, 13 could be identified upon digestion and MALDI-TOF, MS analysis. In addition, the strong modulation of cystatin C was also confirmed by immunoblot analysis and the highly altered level of the 14-3-3 proteins that escaped detection by 2-D mapping, could be assessed by Western blots and immuno-detection of monomeric and homo- and hetero-dimeric 14-3-3 isotypes. In search for a panel of potential markers for sCJD, we highlight cystatin C, 14-3-3 proteins, transferrin, ubiquitin, Apoliprotein J and perhaps some of the still unidentified, but strongly modulated polypeptide chains detected in the differential map.
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PMID:Searching for markers of Creutzfeldt-Jakob disease in cerebrospinal fluid by two-dimensional mapping. 1651 11

In this study, a full-length cytosolic heat shock protein 70 complementary DNA (cDNA) of Laminaria japonica (designated as LJHsp70) was obtained by reverse transcriptase-polymerase chain reaction (RT-PCR) coupled with rapid amplification of cDNA ends. The full length of LJHsp70 cDNA was 2,918 bp, with a 5' untranslated region of 248 bp, a 3' untranslated region of 696 bp, and an open reading frame of 1,974 bp encoding a polypeptide of 657 amino acids with an estimated molecular mass of 72.03 kDa and an estimated isoelectric point of 4.97. There was highly repeated sequence of CAA in 5' untranslated region of LJHsp70. The result of phylogenetic tree of Hsp70s, the BLAST program, analysis and cytosolic Hsp70-specific motif of LJHsp70 verified that the cloned LJHsp70 belonged to cytosolic Hsp70 family. Three typical Hsp70 signature motifs were detected in LJHsp70 by InterPro analysis. Under different stress conditions, messenger RNA (mRNA) expression levels of LJHsp70 were quantified by quantitative RT-PCR. To L. japonica sporophytes kept in different temperatures for 1 h, the expression level of LJHsp70 at 30 degrees C was highest and twofold higher than that at 10 degrees C. To L. japonica sporophytes kept at 25 degrees C for different times, the mRNA expression level of LJHsp70 reached a maximum level after 7 h and then dropped progressively. The expression level of LJHsp70 at 0 or 5 per thousand salt concentration for 2 h was twofold higher than that at 30 per thousand salt concentration for 2 h. The results showed that LJHsp70 may be a kind of potential biomarker used to monitor environment conditions.
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PMID:Molecular cloning and expression analysis of a cytosolic Hsp70 gene from Laminaria japonica (Laminariaceae, Phaeophyta). 1925 34


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