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)

Myeloid-related protein 14 (MRP-14) and its heterodimeric partner, MRP-8, are cytosolic calcium-binding proteins, highly expressed in neutrophils and monocytes. To understand the function of MRP-14, we performed targeted disruption of the MRP-14 gene in mice. MRP-14(-/-) mice showed no obvious phenotype and were fertile. MRP-8 mRNA but not protein is present in the myeloid cells of these mice, suggesting that the stability of MRP-8 protein is dependent on MRP-14 expression. A compensatory increase in other proteins was not detected in cells lacking MRP-8 and MRP-14. Although the morphology of MRP-14(-/-) myeloid cells was not altered, they were significantly less dense. When Ca(2+) responses were investigated, there was no change in the maximal response to the chemokine MIP-2. At lower concentrations, however, there was reduced responsiveness in MRP-14(-/-) compared with MRP-14(+/+) neutrophils. This alteration in the ability to flux Ca(2+) did not impair the ability of the MRP-14(-/-) neutrophils to respond chemotactically to MIP-2. In addition, the myeloid cell functions of phagocytosis, superoxide burst, and apoptosis were unaffected in MRP-14(-/-) cells. In an in vivo model of peritonitis, MRP-14(-/-) mice showed no difference from wild-type mice in induced inflammatory response. The data indicate that MRP-14 and MRP-8 are dispensable for many myeloid cell functions.
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PMID:Myeloid cell function in MRP-14 (S100A9) null mice. 1264 Jan 37

S100A12 is a member of the S100 family of EF-hand calcium-binding proteins. Together with two other calgranulins, S100A8 and S100A9, it is mostly expressed in human granulocytes, although there is increasing evidence of expression in keratinocytes and psoriatic lesions. It is involved in host-parasite response, and linked to corneal autoimmune diseases connected with filarial parasite infestation. Interaction of S100A12 with a multiligand receptor for advanced glycation end products (RAGE) mediates inflammation. Human recombinant S100A12 was found to induce neuritogenesis of cultured hippocampal cells, similar to two other S100 proteins, S100B and S100A4. X-ray structure of S100A12 has been solved in two crystal forms: R3 and P2(1). In the R3 crystal form S100A12 is a dimer, and in the P2(1) crystal form the dimers are arranged as a hexamer. The hexameric form suggests its role in receptor oligomerisation. S100A12 binds copper at the predicted zinc/copper binding site, which is located close to the surface of the protein. We propose copper-mediated generation of reactive oxygen species by S100A12 as its function in host-parasite response.
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PMID:Multiple structural states of S100A12: A key to its functional diversity. 1264 6

Three members of the S100 family of calcium-binding proteins comprise a new group of proinflammatory molecules released by phagocytes. A novel inflammatory syndrome defined by extraordinarily high expression of S100A8 and S100A9 confirmed recent observations in vitro demonstrating a role of these proteins during recruitment of leukocytes. S100A12 directly activates endothelial cells, mononuclear phagocytes and lymphocytes through interaction with the receptor for advanced glycation end products. Thus, these S100-proteins are attractive targets to modulate inflammation.
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PMID:Phagocyte-specific S100 proteins: a novel group of proinflammatory molecules. 1269 38

S100 proteins are calcium-activated signaling proteins that interact with target proteins to modulate biological processes. Our present studies compare the level of expression, and cellular localization of S100A7, S100A8, S100A9, S100A10, and S100A11 in normal and psoriatic epidermis. S100A7 and S100A11 are present in the basal and spinous layers in normal epidermis. These proteins appear in the nucleus and cytoplasm in basal cells but are associated with the plasma membrane in spinous cells. S100A10 is present in basal and spinous cells, in the cytoplasm, and is associated with the plasma membrane. S100A8 and S100A9 are absent or are expressed at minimal levels in normal epidermis. In involved psoriatic tissue, S100A10 and S100A11 levels remain unchanged, whereas, S100A7, S100A8, and S100A9 are markedly overexpressed. The pattern of expression and subcellular localization of S100A7 is similar in normal and psoriatic tissue. S100A8 and S100A9 are strongly expressed in the basal and spinous layers in psoriasis-involved tissue. In addition, we demonstrate that S100A7, S100A10, and S100A11 are incorporated into detergent and reducing agent-resistant multimers, suggesting that they are in vivo transglutaminase substrates. S100A8 and S100A9 did not form these larger complexes. These results indicate that S100 proteins localize to the plasma membrane in differentiated keratinocytes, suggesting a role in regulating calcium-dependent, membrane-associated events. These studies also indicate, as reported previously, that S100A7, S100A8, and S100A9 expression is markedly altered in psoriasis, suggesting a role for these proteins in disease pathogenesis.
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PMID:S100 protein subcellular localization during epidermal differentiation and psoriasis. 1270 15

S100A12 is a member of the S100 family of EF-hand calcium-modulated proteins. Together with S100A8 and S100A9, it belongs to the calgranulin subfamily, i.e. it is mainly expressed in granulocytes, although there is an increasing body of evidence of expression in keratinocytes and psoriatic lesions. As well as being linked to inflammation, allergy and neuritogenesis, S100A12 is involved in host-parasite response, as are the other two calgranulins. Recent data suggest that the function of the S100-family proteins is modulated not only by calcium, but also by other metals such as zinc and copper. Previously, the structure of human S100A12 in low-calcium and high-calcium structural forms, crystallized in space groups R3 and P2(1), respectively, has been reported. Here, the structure of S100A12 in complex with copper (space group P2(1)2(1)2; unit-cell parameters a = 70.6, b = 119.0, c = 90.2 A) refined at 2.19 A resolution is reported. Comparison of anomalous difference electron-density maps calculated with data collected with radiation of wavelengths 1.37 and 1.65 A shows that each monomer binds a single copper ion. The copper binds at an equivalent site to that at which another S100 protein, S100A7, binds zinc. The results suggest that copper binding may be essential for the functional role of S100A12 and probably the other calgranulins in the early immune response.
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PMID:Structure of the human S100A12-copper complex: implications for host-parasite defence. 1277 2

In order to understand the mechanisms underlying the development of resistance to a pure antiestrogen we established three human breast carcinoma cell lines resistant to ZM 182780 (ZM) (Faslodex). Long-term cultivation of the ERalpha-positive, 17beta-estradiol (E(2))-responsive cell lines T47D, ZR-75-1, and MCF-7 with the pure antiestrogen ZM 182780 resulted in the T47D-r, ZR-75-1-r, and MCF-7-r cell lines, which proliferate continuously in the presence of 10(-6)M ZM 182780. The resulting antiestrogen-resistant cells grow equally well in medium with or without E(2) and in medium with or without ZM 182780 indicating that they are no longer estrogen-responsive. ERalpha expression was lost at the protein level in all three resistant cell lines. At the mRNA level, the ERalpha was only faintly detectable in T47D-r, whereas a weak signal was seen in ZR-75-1-r and MCF-7-r. By reverse transcription-polymerase chain reaction (RT-PCR) the ERbeta was detectable in the antiestrogen-sensitive and -resistant breast cancer cell lines, however, ZR75-1-r contained the smallest signal for ERbeta. In all three antiestrogen-resistant cells the PR was undetectable, whereas binding of epidermal growth factor (EGF) and protein expression of epidermal growth factor receptor (EGFR) were increased. To analyse alterations in the gene expression pattern in more detail Atlas arrays were hybridised with RNA isolated from T47D-r and T47D and the two Ca2+-binding proteins calgranulin A and B were found to be up-regulated in T47D-r compared to T47D. Calgranulin A and B were also both up-regulated in ZR-75-1-r and MCF-7-r compared to their antiestrogen-sensitive counterparts. Loss of ERalpha expression may be linked to the acquisition of antiestrogen resistance and enhanced expression of the EGFR and of proteins of the S100 family of Ca2+-binding proteins which may contribute to the outgrowth of resistant cells.
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PMID:Studies on the development of resistance to the pure antiestrogen Faslodex in three human breast cancer cell lines. 1279 55

To identify genes that are differentially expressed in human esophageal squamous cell carcinoma (ESCC), we have developed a cDNA microarray representing 34 176 clones to analyse gene expression profiles in ESCC. A total of 77 genes (including 31 novel genes) were downregulated, and 15 genes (including one novel gene) were upregulated in cancer tissues compared with their normal counterparts. Immunohistochemistry and Northern blot analysis were carried out to verify the cDNA microarray results. It was revealed that genes involved in squamous cell differentiation were coordinately downregulated, including annexin I, small proline-rich proteins (SPRRs), calcium-binding S100 proteins (S100A8, S100A9), transglutaminase (TGM3), cytokeratins (KRT4, KRT13), gut-enriched Krupple-like factor (GKLF) and cystatin A. Interestingly, most of the downregulated genes encoded Ca(2+)-binding or -modulating proteins that constitute the cell envelope (CE). Moreover, genes associated with invasion or proliferation were upregulated, including genes such as fibronectin, secreted protein acidic and rich in cystein (SPARC), cathepsin B and KRT17. Functional analysis of the alteration in the expression of GKLF suggested that GKLF might be able to regulate the expression of SPRR1A, SPRR2A and KRT4 in ESCC. This study provides new insights into the role of squamous cell differentiation-associated genes in ESCC initiation and progression.
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PMID:Discovery of Ca2+-relevant and differentiation-associated genes downregulated in esophageal squamous cell carcinoma using cDNA microarray. 1464 9

Methylenetetrahydrofolate reductase (MTHFR) deficiency is the most common genetic cause of hyperhomocysteinemia, which is associated with increased risk for cardiovascular disease, stroke and possibly other neurological disorders. Microarray analysis of brain RNA from day 14 Mthfr(-/-) mice revealed several genes with altered expression. Expression changes in inositol 1,4,5-triphosphate receptor, type 1 (Itpr1), proteolipid protein (Plp), neurogenic differentiation factor 1 (Neurod1), S100 calcium binding protein A8 (S100a8), and methylenetetrahydrofolate dehydrogenase (NAD+ dependent), methenyltetrahydrofolate cyclohydrolase (Mthfd2) were confirmed by RT-PCR. We propose that neuronal damage by hyperhomocysteinemia may involve disruption of intracellular calcium.
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PMID:Microarray analysis of brain RNA in mice with methylenetetrahydrofolate reductase deficiency and hyperhomocysteinemia. 1501 4

The EF-hand homolog family of S100 proteins comprises the largest group of calcium-binding proteins. Within this S100 family, the phagocyte-specific calcium-binding proteins are pro-inflammatory molecules expressed and secreted by phagocytes, which play a pivotal role within the innate immune system. Although the exact biological functions of these proteins still remain to be defined in greater detail, there is evidence that they are involved in a pro-inflammatory axis associated with various inflammatory conditions. The three members of this group, S100A8, S100A9 and S100A12 are overexpressed at local sites of inflammation. High concentrations are found in synovial fluid, sputum, stool and blood plasma/serum during inflammation. Both the S100A8/S100A9 complex and S100A12 have been proven to be useful as diagnostic markers of inflammation especially in non-infectious inflammatory diseases such as arthritis, chronic inflammatory lung and bowel disease. They indicate phagocyte activation more sensitively than conventional parameters of inflammation. As a consequence, there is a strong correlation to the inflammation of various acute and chronic disorders, making these proteins sensitive parameters for the monitoring of disease activity and response to treatment in individual patients. The phagocyte-specific S100 proteins are able to indicate minimal residual inflammation, which is not detected by other diagnostic tests, and they may even be prospective markers for the outcome of patients. In this review, pro-inflammatory functions of S100 proteins and their usefulness as biomarkers of inflammation are presented.
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PMID:Phagocyte-specific calcium-binding S100 proteins as clinical laboratory markers of inflammation. 1514 69

The S100 proteins comprise a family of 21 low molecular weight (9-13 kDa) proteins that are characterized by the presence of two calcium-binding EF-hand motifs. Fourteen S100 protein genes are located within the epidermal differentiation complex on human chromosome 1q21 and 13 S100 proteins (S100A2, S100A3, S100A4, S100A6, S100A7, S100A8, S100A9, S100A10, S100A11, S100A12, S100A15, S100B, and S100P) are expressed in normal and/or diseased epidermis. S100 proteins exist in cells as anti-parallel hetero- and homodimers and upon calcium binding interact with target proteins to regulate cell function. S100 proteins are of interest as mediators of calcium-associated signal transduction and undergo changes in subcellular distribution in response to extracellular stimuli. They also function as chemotactic agents and may play a role in the pathogenesis of epidermal disease, as selected S100 proteins are markedly overexpressed in psoriasis, wound healing, skin cancer, inflammation, cellular stress, and other epidermal states.
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PMID:S100 proteins in the epidermis. 1519 38


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