Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05109 (S100A8)
 1,212 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chromosome 1 reveals in region 1q21 a most remarkable density of genes that fulfill important functions in terminal differentiation of the human epidermis. These genes encode the cornified envelope precursors loricrin, involucrin, and small proline-rich proteins (SPRR1, SPRR2, and SPRR3), the intermediate filament-associated proteins profilaggrin and trichohyalin, and several S100A calcium-binding proteins. Extending and refining our previous physical map of 1q21 we have now mapped two additional S100A genes as well as the three SPRR subfamilies and resolved the arrangement of involucrin, SPRRs, and loricrin. All genes are linked within 1.9 Mbp of human genomic DNA in the order: S100A10, trichohyalin, profilaggrin, involucrin, SPRR3, SPRR1B, SPRR2A, loricrin, S100A9, S100A9, S100A8, S100A6. Colocalization of genes expressed late during maturation of epidermal cells together with genes encoding calcium-binding proteins is particularly intriguing since calcium levels tightly control the differentiation of epithelial cells and the expression of genes encoding epidermal structural proteins. Accounting for the close functional cooperation among these structurally and evolutionary related genes, we conclude that these loci constitute a gene complex, for which we propose the name epidermal differentiation complex.
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PMID:Genes encoding structural proteins of epidermal cornification and S100 calcium-binding proteins form a gene complex ("epidermal differentiation complex") on human chromosome 1q21. 861 63

We found by using a 45Ca2+ overlay technique a large amount of Ca(2+)-binding activity in bovine amniotic fluid from which a novel calcium-binding protein (CaBP) was purified and is referred to as CAAF1 (calcium-binding protein in amniotic fluid-1), with an apparent molecular mass of 8 kDa determined by N-tris(hydroxymethyl)-methylglycine/ SDS-PAGE. It was structurally homologous with MRP/calgranulin proteins (MRP8/calgranulin A and MRP14/calgranulin B), members of the S100 protein family, which are abundantly found in the cytoplasm of granulocytes and macrophages. CAAF1 lacked the predicted signal peptide sequence, which is consistent with other CaBPs. The tissue and cellular distribution of CAAF1 was determined by monoclonal antibodies developed against this protein. Its immunoreactivity was found in squamous epithelial cells, neutrophils, and some macrophages throughout the fetal body. An especially characteristic staining pattern was obtained in the squamous epithelium, including that of the esophagus, skin and amnion: CAAF1 was detected in the suprabasal squamous epithelial cells undergoing differentiation, but not in the cells in the proliferating basal layer. Northern blot analysis also showed that CAAF1 mRNA was highly expressed in bovine fetal esophagus and skin. On the other hand, our ELISA studies showed that CAAF1 protein was present in amniotic fluid at a concentration of about 120 nM, which was over 30 times as high as that in the fetal serum. These results suggested that CAAF1 is one of the stage-specific proteins in the differentiation of squamous epithelial cells, and that CAAF1 is preferentially produced by fetal squamous epithelial cells, including epidermal keratinocytes and amniotic epithelial cells, and it is stored in the amniotic fluid during embryogenesis.
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PMID:A novel calcium-binding protein in amniotic fluid, CAAF1: its molecular cloning and tissue distribution. 871 72

Inverse agonists are ligands that are capable of repressing basal receptor activity in the absence of an agonist. We have designed a series of C-1-substituted acetylenic retinoids that exhibit potent antagonism of retinoic acid receptor (RAR)-mediated transactivation. Comparison of these related retinoid antagonists for their ability to repress basal RAR transcriptional activity demonstrates that the identity of the C-1 substituent differentiates these ligands into two groups: RAR inverse agonists and neutral antagonists. We show that treatment of cultured human keratinocytes with a RAR inverse agonist, but not a RAR neutral antagonist, leads to the repression of the serum-induced differentiation marker MRP-8. While RAR-selective agonists also repress expression of MRP-8, cotreatment with a RAR inverse agonist and a RAR agonist results in a mutual repression of their individual inhibitory activities, indicating the distinct modes of action of these two disparate retinoids in modulating MRP-8 expression. Our data indicate that RARs, like beta2-adrenoreceptors, are sensitive to inverse agonists and that this new class of retinoids will provide insight into the molecular mechanisms of RAR function in skin and other responsive tissues.
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PMID:Identification and functional separation of retinoic acid receptor neutral antagonists and inverse agonists. 879 42

The myeloid-related proteins MRP-14 and MRP-8 and also p6, three calcium-binding proteins of the S100 family, translocate to the membrane during human neutrophil activation with stimuli known to require extracellular calcium for activity. When phorbol 12-myristate 13-acetate (PMA, an extracellular calcium-independent stimulus) is used, no translocation is observed. To characterize further the mechanisms involved in their translocation, phosphorylation of these proteins was studied. Three isoforms of MRP-14 were markedly phosphorylated in the membrane and in the cytosol upon activation with extracellular calcium-dependent stimuli, such as opsonized zymosan, the calcium ionophore A23187, N-formylmethionylleucylphenylalanine in the presence of cytochalasin B and arachidonic acid, or upon extracellular calcium-independent stimulation (PMA). In no case were p6 and a fourth, more basic isoform of MRP-14, phosphorylated. In PMA-activated cells, a phosphorylated acidic isoform of MRP-8 was detected in the cytosol only. However, phosphorylated MRP-8 represented only a small fraction of total MRP-8. Cgp 41251, an inhibitor of protein kinase C (PKC), completely inhibited the phosphorylation of MRP-8, and decreased cytosolic MRP-14 phosphorylation. To test whether phosphorylated MRP-8 could translocate, A23187, which induces translocation of the three S100 proteins, was added after PMA activation. This resulted in translocation of 18% +/- 5% of phosphorylated MRP-14 and 19% +/- 1% of only nonphosphorylated MRP-8. However, upon inhibition of PKC, translocation of MRP-14 and MRP-8 was increased up to 38% +/- 7% and 34% +/- 3% respectively. This suggests a putative role of phosphorylation and/or of PKC in the modulation of MRP-14 and MRP-8 translocation to the membrane.
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PMID:Phosphorylation of myeloid-related proteins MRP-14 and MRP-8 during human neutrophil activation. 889 15

Mac 387, a murine mAb, was previously described to detect a complex form of MRP-14 and MRP-8, two calcium-binding proteins of the S100 family, but recent experiments suggested that Mac 387 recognized only MRP-14. Using two-dimensional polyacrylamide gel electrophoresis and the very sensitive enhanced chemiluminescence detection system, the immunoreactivity of Mac 387 was compared with that of a polyclonal antibody raised against purified MRP-8, but cross-reacting with MRP-14 and p6, a novel S100 protein. Under such conditions, Mac 387 was found to recognize the three S100 proteins. This result suggests that Mac 387 might recognize an epitope common of the proteins of the S100 family.
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PMID:The monoclonal antibody Mac 387 recognizes three S100 proteins in human neutrophils. 893 61

The epidermal differentiation complex (EDC) unites a remarkable number of structurally, functionally, and evolutionarily related genes that play an important role in terminal differentiation of the human epidermis. It is localized within 2.05 Mb of region q21 on human chromosome 1. We have identified and characterized 24 yeast artificial chromosome (YAC) clones by mapping individual EDC genes, sequence-tagged site (STS) markers (D1S305, D1S442, D1S498, D1S1664), and 10 new region-specific probes (D1S3619-D1S3628). Here we present a contig that covers about 6 Mb of 1q21 including the entire EDC. Fluorescence in situ hybridization on metaphase chromosomes with two YACs flanking the EDC determined its chromosomal orientation and established, in conjunction with physical mapping results, the following order of genes and STSs: 1cen-D1S442-D1S498-S100A10-THH-FLG- D1S1664-IVL-SPRR3-SPRR1-SPRR2-LOR- S100A9-S100A8-S100A7-S100A6-S100A5-S100 A4- S100A3-S100A2-S100A1-D1S305-1qtel. These integrated physical, cytogenetic, and genetic mapping data will be useful for linkage analyses of diseases associated with region 1q21 and for the identification of novel genes and regulatory elements in the EDC.
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PMID:Genetic analysis of the epidermal differentiation complex (EDC) on human chromosome 1q21: chromosomal orientation, new markers, and a 6-Mb YAC contig. 893 41

Retinoids down-regulate the expression of metalloproteinases, cytokines, and other genes involved in cell proliferation and inflammation. Tazarotene (AGN 190168), a retinoic acid receptor (RAR)-specific retinoid, is effective in the treatment of psoriasis, a hyperproliferative and inflammatory skin disease. Because negative regulation of genes appears to be important in the antiproliferative and antiinflammatory action of retinoids, we studied the down-regulation of genes in skin raft cultures by this antipsoriatic retinoid. By subtraction hybridization, we found that migration inhibitory factor-related protein (MRP-8) and skin-derived anti-leukoproteinase (SKALP) are down-regulated by AGN 190168. MRP-8 and SKALP are overexpressed in psoriatic lesions as compared to the normal epidermis, and they are markers of hyperproliferative keratinocyte differentiation. We also show that MRP-8 expression is retinoid inhibitable in cultured keratinocytes induced to differentiate with 10% serum or IFN-gamma, and that MRP-8 is inhibited by RAR but not by retinoid X receptor-specific retinoids in a dose-dependent manner. Finally, MRP-8, SKALP, and the previously characterized differentiation marker, transglutaminase I, are all down-regulated in vivo in psoriatic lesions after treatment with AGN 190168 in comparison to placebo. Taken together, these data suggest that these markers may be down-regulated by tazarotene in psoriasis through direct action on keratinocyte gene expression rather than by an overall tazarotene effect on lesional therapeutic status.
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PMID:Negative regulation of two hyperproliferative keratinocyte differentiation markers by a retinoic acid receptor-specific retinoid: insight into the mechanism of retinoid action in psoriasis. 895 47

We developed a quantitative enzyme immunoassay for human MRP-8/MRP-14, neutrophil cytosolic proteins with calcium-binding and bacteriastatic properties. MRP-8/MRP-14 concentrations were measured in the plasma of 23 healthy volunteers and in 75 patients with hematological disorders. These proteins were detected in plasma of healthy blood donors with mean +/- standard deviation 167 +/- 114 ng/ml. MRP-8/MRP-14 plasma levels ranged from 435 to 13280 ng/ml in patients with chronic myeloid leukemia (CML), from 50 to 7570 ng/ml in chronic lymphoid leukemia (CLL), from 450 to 2790 ng/ml in polycythemia vera (PV), and were significantly higher than in healthy blood donors (P < 0.01 for CML and P < 0.05 for others). In CML patients MRP-8/MRP-14 levels strongly correlated with total blood WBC count (r = 0.82) and with neutrophilic granulocyte (NG) count (r = 0.80). Correlation of these values in PV amounted to r = 0.70 and r = 0.46, respectively. In CLL patients MRP-8/MRP-14 levels strongly correlated with total WBC count (r = 0.92), but not with the NG count. We suggest that MRP-8/MRP-14 quantitation may serve as a marker of neutrophil pool turnover in some hematological disorders.
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PMID:Enzyme-linked immunosorbent assay for human MRP-8/MRP-14 proteins and their quantitation in plasma of hematological patients. 896 12

Here, we report the characterization of a human cDNA coding for the recently published amino acid sequence of a calcium-binding S100 protein, S100A12 (CGRP, calgranulin C, CAAF1, p6). The exon/intron structure of the S100A12 gene is similar to most other S100 genes. It is composed of three exons which are divided by two introns of 900 bp and 400 bp. The protein is encoded by sequences in exons 2 and 3, with exon 2 coding for the N-terminal 45 amino acids and exon 3 coding for the C-terminal 46 amino acids. So far, ten S100 genes are known to be located on human chromosome 1q21 in a clustered organization. Hence, we investigated whether S100A11 (S100C, calgizzarin) and S100A12 are also localized in the S100 gene cluster. We found both genes within the cluster, with S100A11 being close to S100A10 and S100A12 between the genes S100A8 and S100A9. Therefore, the S100 gene cluster now is composed of 12 differentially expressed family members.
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PMID:Characterization of the human S100A12 (calgranulin C, p6, CAAF1, CGRP) gene, a new member of the S100 gene cluster on chromosome 1q21. 898 90

So far, microglial activation in cerebral ischemia has only been studied in different animal models. We have investigated the activation of microglial cells in human cerebral ischemia. As a marker for the activation of these "brain macrophages," we have used the macrophage inhibitor factor-related-proteins MRP-8 and MRP-14, which belong to the calcium binding S-100 protein family. The proteins can be detected on microglial cells in bacterial encephalitis and Alzheimer's disease but have so far not been studied in non-inflammatory diseases, in which microglial activation also occurs. Antibodies against MRP-8 and -14 detected ramified microglial cells within the first 3 days after cerebral infarction. Labeled cells were found selectively in the periinfarctional area. To support the notion that these cells belong to the locally activated resident microglial population, we studied their proliferation rate by staining the Ki-67 antigen with the antibody MIB-1. Double-labeling clearly showed that in the early phase of cerebral infarction microglial cells in the periinfarctional area express MRP-8 and -14 and also proliferate. Surprisingly, MRPs are expressed no longer than 3 days post infarction. This indicates that the activation of the resident microglia is an early step of tissue reaction after cerebral infarction. Additionally, we found evidence that microglial cells contribute to the population of phagocytes only during the first 3 days post infarction. The majority of lipid phagocytes found in the later stages are obviously recruited from the blood-borne macrophage pool.
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PMID:Expression of the S-100 proteins MRP-8 and -14 in ischemic brain lesions. 898 65


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