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

In the implantation, trophoblasts penetrate maternal decidua by secreting proteases. It has been reported that cathepsins are highly expressed in the mouse villi, and play an important role in normal embryonal growth and decidualization. In this study, we evaluated cathepsins and their endogenous inhibitors, cystatins, in tissue and serum of patients with recurrent miscarriage. Decidua and villi were surgically collected from 22 patients and 12 healthy women. Immunohistochemistry was performed with antibodies against cathepsins, stefin A (cystatin A), stefin B (cystatin B) and cystatin C. The concentrations of cathepsins, stefins and cystatin C were measured by Enzyme-linked immunosorbent assay. In addition, we measured the serum level of cystatin C in 85 Japanese women with recurrent miscarriage. Staining of cathepsin B, D, H, L, stefin B and cystatin C was observed in the cytoplasm of epithelial cells in decidua. Stefin A was expressed on the surface of the trophoblast. The concentration of cathepsin B and H in patients' decidua was significantly higher than in control individuals. The serum level of cystatin C was significantly lower in patients than in control individuals. Our findings suggest that the regulation of the cathepsin-cystatin system may play an important role in patients with recurrent miscarriage.
Mol Hum Reprod 2005 May
PMID:Role of cathepsins and cystatins in patients with recurrent miscarriage. 1586 50

Nogo is a myelin-associated protein associated with neurite outgrowth and regeneration. A previous study has reported an association between an insertion/deletion polymorphism in schizophrenia. We tested for the distribution of the polymorphism and haplotypes of this and another insertion/deletion polymorphism in our population. We have also developed an assay combining allele-specific polymerase chain reaction (AS-PCR) and restriction fragment length polymorphism (RFLP) to simultaneously type these two insertion/deletion polymorphisms. There was a statistically significant difference at the allelic level for both the CAA (chi2 = 4.378, df = 1, P value = 0.036) and TATC (chi2 = 5.807, df = 1, P = 0.016) polymorphisms in the female subgroup, but not in males. With our genotyping method, we also determined the molecular haplotype. Within the female gender, odds ratio is at 1.57 (95% CI 1.05-2.37) for CAACAA-TATC and 1.40 (95% CI 0.55-3.60) for CAA-TATC, the two at-risk haplotypes. Odds ratio is 0.63 (95% CI 0.42-0.93) for the protective wildtype haplotype CAA-TATCTATC. Further study of these two polymorphisms to investigate functional significance and confirm gender-specific association should be carried out.
Brain Res Mol Brain Res 2005 Oct 03
PMID:Gender-specific association of insertion/deletion polymorphisms in the nogo gene and chronic schizophrenia. 1595 57

Cerebral amyloid angiopathy (CAA) results from amyloid accumulation within arteries of the cerebral cortex and leptomeninges. This condition is age-related, especially prevalent in Alz-heimer's disease (AD), and the main feature of certain hereditary disorders (i.e., HCHWA-I). The vascular smooth muscle cells (VSMCs) appear to play a vital role in the development of CAA, which makes them well-suited as an experimental model to study the disease and screen for possible remedies. We describe two different methods for isolating and culturing human VSMCs. First, using the human umbilical cord as an easy source of robust cells, and secondly, using brain tissue that provides the proper cerebral VSMCs, but is more problematic to work with. Finally the maintenance, preservation, and characterization of the isolated VSMCs are described.
Methods Mol Biol 2005
PMID:Isolation and culturing of human vascular smooth muscle cells. 1598 Jun 3

The characterization of proteins in their native state is essential for the understanding of patho-genic isoforms. A variant of the cysteine protease inhibitor cystatin C is the major constituent of the amyloid deposited in the cerebral vasculature of patients with the Icelandic form of hereditary cerebral hemorrhage with amyloidosis (HCHWA-I). In order to study the nature of the bio-physical changes owing to the Leu68Gln substitution in cystatin C, we have developed a purification procedure of human cystatin C in its native state. The protein is isolated from media of stably transfected tissue culture cells using physiological conditions that preclude protein denaturation. The importance of mild purification conditions is underscored by the finding that denaturation of the wild-type and variant proteins facilitates a similar folding of both molecules, diminishing their differences in structure and biophysical properties. Following native purification conditions, variant cystatin C has a distinct structure compared to the wild-type protein.
Methods Mol Biol 2005
PMID:Purification of human wild-type or variant cystatin C from conditioned media of transfected cells. 1598 Jun 5

PDK-1 is a protein kinase that is critical for the activation of many downstream protein kinases in the AGC superfamily, through phosphorylation of the activation loop site on these substrates. Cells lacking PDK-1 show decreased activity of these protein kinases, including protein kinase B (PKB) and p70S6K, whereas mTOR activity remains largely unaffected. Here we show, by assessing both association of cellular RNAs with polysomes and by metabolic labeling, that PDK-1-/- embryonic stem (ES) cells exhibit defects in mRNA translation. We identify which mRNAs are most dramatically translationally regulated in cells lacking PDK-1 expression by performing microarray analysis of total and polysomal RNA in these cells. In addition to the decreased translation of many RNAs, a smaller number of RNAs show increased association with polyribosomes in PDK-1-/- ES cells relative to PDK-1+/+ ES cells. We show that PKB activity is a critical downstream component of PDK-1 in mediating translation of cystatin C, RANKL, and Rab11a, whereas mTOR activity is less important for effective translation of these targets.
Mol Cell Biol 2005 Oct
PMID:Translational deregulation in PDK-1-/- embryonic stem cells. 1616 29

Affinity mass spectrometry (AMS) is a proteomics approach for selectively isolating target protein(s) from complex biological fluids for mass spectrometric analysis. The resulting high-content mass spectrometry (MS) data show the unique MS protein signatures (wild-type, posttranslationally modified, as well as genetically modified forms of the protein target) that are present within a biological sample. Information regarding such protein diversity is normally lost in classical proteomic or immunoassay analyses. This chapter presents a step-by-step description of high-throughput AMS in the population proteomic screening of the human plasma protein cystatin C.
Methods Mol Biol 2006
PMID:High-throughput affinity mass spectrometry. 1678 46

The Dictyostelium discoideum genome has been sequenced, assembled and annotated to a high degree of reliability. The parts-list of proteins and RNA encoded by the six chromosomes can now be accessed and analyzed. One of the initial surprises was the remarkably large number of genes that are shared with plants, animals, and fungi that must have been present in their common progenitor over a billion years ago. The genome encodes a total of about 10,300 proteins including protein families involved in cytoskeletal control, posttranslational protein modification, detoxification, secondary metabolism, cell adhesion, and signal transduction. The genome has a higher proportion of homopolymeric tracts and simple sequence repeats, such as [CAA]n, than most other genomes. Triplet repeats in translated regions produce the highest known proportion of polyglutamine tracts in any known proteome. Phylogenetic analyses based on complete proteomes confirm that the amoebozoa are a sister group to the animals and fungi, distinct from plants and early diverging species such as Leishmania, Plasmodium, or Giardia. The completed Dictyostelium sequence opens the door to large-scale functional exploration of its genome.
Methods Mol Biol 2006
PMID:The Genome of Dictyostelium discoideum. 1695 82

Here we present the tetrameric structure of stefin B, which is the result of a process by which two domain-swapped dimers of stefin B are transformed into tetramers. The transformation involves a previously unidentified process of extensive intermolecular contacts, termed hand shaking, which occurs concurrently with trans to cis isomerization of proline 74. This proline residue is widely conserved throughout the cystatin superfamily, a member of which, human cystatin C, is the key protein in cerebral amyloid angiopathy. These results are consistent with the hypothesis that isomerization of proline residues can play a decisive role in amyloidogenesis.
J Mol Biol 2007 Mar 09
PMID:Essential role of proline isomerization in stefin B tetramer formation. 1721 64

Trophoblast invasion is regulated by proteinases and their inhibitors. Cystatin C inhibits cysteine proteinases. The serum concentration of cystatin C is increased in late pregnancy and pre-eclampsia. We aimed to investigate whether the expression of cystatin C is increased in the pre-eclamptic placenta and to investigate the expression pattern of cystatin C mRNA and protein in placental tissue. Tissue samples from the central part of the placenta from 13 normal and 22 pre-eclamptic pregnancies were included. We used real-time polymerase chain reaction (RT-PCR) and in situ hybridization for mRNA expression analysis and immunohistochemistry and Western blotting for protein expression analysis. RT-PCR showed a significantly higher expression of cystatin C mRNA in pre-eclampsia than in normal pregnancy, with the highest expression in cases with severe pre-eclampsia. In situ hybridization revealed a distinct pattern of high expression in the extravillous trophoblast cells of the basal plate and low expression in the syncytiotrophoblast covering villi. The cystatin C protein distribution matched the mRNA expression pattern. Western blot analysis revealed an increased protein expression in cases with severe pre-eclampsia and confirmed the presence of cystatin C in amniotic fluid samples. The high expression of cystatin C mRNA in the extravillous trophoblast cells of the basal plate suggests a role for cystatin C in the regulation of proteases in placentation. Placental expression and secretion of cystatin C could contribute to the elevated maternal plasma levels seen in pre-eclampsia.
Mol Hum Reprod 2007 Mar
PMID:Increased cystatin C expression in the pre-eclamptic placenta. 1722 16

Chicken cystatin, a homologue of human cystatin C, like other low-molecular-weight proteins is metabolized by renal proximal tubule cells. However, the precise mechanism(s) of this process has not been elucidated yet. To characterize chicken cystatin binding to renal brush-border membranes, the incubation of fluorescein labelled protein with rat cortical homogenate was performed. Saturation-dependent and reversible binding with low affinity (K(d)=3.67-4.07 microM) and high capacity (B(max)=2.32-2.79 nmol/mg) was observed. Bovine albumin was the most potent competitor (K(i)=0.7 microM) among other megalin/cubilin ligands tested. The presence of Ca(+2) ions was necessary to effective cystatin binding by brush-border membranes. Obtained data strongly support the hypothesis that chicken cystatin is a novel ligand for megalin/cubilin receptors tandem on proximal tubular cells.
Comp Biochem Physiol B Biochem Mol Biol 2007 Apr
PMID:Characterization of chicken cystatin binding to rat renal brush-border membranes. 1727 77


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