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)

This article presents new information regarding the complement/level of S100 family members expressed in the brain and reviews the contribution of brain S100 family members to nervous system function and disease. A total of ten S100 family members are reported in the literature to be expressed in brain -S100A1, S100A2, S100A4, S100A5, S100A6, S100A10, S100A11, S100A13, S100B, and S100Z. Quantitative Northern blot analysis detected no S100A3, S100A8, S100A9 or S100A14 mRNA in mouse brain suggesting that these family members are not expressed in the brain. In addition, there was a 100-fold range in the mRNA levels for the six family members that were detected in mouse brain: S100A1/S100B levels were 5-fold higher than S100A6/S100A10 levels and 100-fold higher than S100A4/S100A13 levels. Five of these six family members (S1100A1, S100A6, S100A10, S100A13, and S100B) exhibited age-dependent increases in expression in adult mice that ranged from 5- to 20-fold. Although previous studies on S100 function in the nervous system have focused on S100B, other family members (S100A1, S100A3, S100A4, S100A5) have been implicated in neurological diseases. Like S100B, intra- and inter-cellular forms of these family members have been linked to cell growth, cell differentiation, and apoptotic pathways. Studies presented here demonstrate that ablation of S100A1 expression in PC12 cells results in increased resistance to Abeta peptide induced cell death, stabilization of intracellular [Ca2+] homeostasis, and reduced amyloid precursor protein expression. Altogether, these results confirm that S100-mediated signal transduction pathways play an important role in nervous system function/disease and implicate S100A1 in the neuronal cell dysfunction/death that occurs in Alzheimer's disease.
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PMID:S100-mediated signal transduction in the nervous system and neurological diseases. 1617 56

Gene expression patterns in ductal carcinoma in situ (DCIS) and invasive and metastatic breast tumors have been determined using serial analysis of gene expression (SAGE). The purpose of this approach was to identify biologically and clinically meaningful subgroups of DCIS with a high risk of progression to invasive disease. The analyses have led to the identification of several differentially expressed genes, such as HIN-1, dermcidin and S100A7 (psoriasin). The aim of the present study was further to delineate the expression profile of S100 genes using information from 22 breast epithelial SAGE libraries. We demonstrated the down-regulation of S100A6 and S100A10 in breast cancer, irrespective of pathological stage. S100P and S100Z were both up-regulated in cancer; whereas S100A7, S100A8 and S100A9 were strongly up-regulated only in DCIS. The hierarchical clustering of S100 gene expression in these 22 libraries revealed two major groups with distinguishable S100 gene expression profiles. One of them was characterized by the high concomitant expression of S100A7, S100A8 and S100A9. Using SAGE informatics, we found 21 genes with a high positive correlation to S100A7 expression in libraries representing different categories of tissues archived at SAGE Genie, suggesting a function of psoriasin that is not tissue specific. Like S100A7, several of these genes displayed cation-binding properties. We also report the strong correlation in the breast epithelial SAGE libraries between the expression of S100A7 and genes reported as being up-regulated in DCIS, as well as in the inflammatory skin disorder, psoriasis; including RGS5, UPK1A, TMPRSS3, S100A9, p53, SCCA1, SCCA2 and KRT17.
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PMID:Cluster analysis of S100 gene expression and genes correlating to psoriasin (S100A7) expression at different stages of breast cancer development. 1627 1

Exposure to oil mist has been associated with a variety of acute and chronic respiratory effects. Using proteomics approaches to investigate exposure-associated proteins may provide useful information to understand the mechanisms of associated respiratory effects. The aim of this study was to investigate changes in rat bronchoalveolar lavage fluid proteins associated with oil mist exposure using nano-HPLC-ESI-MS/MS. The results revealed that 29 proteins exhibited significant changes after exposure. These proteins included surfactant-associated proteins (SP-A and SP-D), inflammatory proteins (complement component 3, immunoglobulins, lysozyme, etc.), growth factors (e.g., transforming growth factor alpha (TGF-alpha)), calcium-binding proteins (calcyclin, calgranulin A, calreticulin, and calvasculin), and other proteins (e.g., cathepsin D, saposin, and intestinal trefoil factor). To further evaluate changes in protein levels, a simple quantitative strategy was developed in this study. A large decrease in protein levels of SP-A and SP-D (0.24- and 0.38-fold, respectively) following exposure was observed. In contrast, protein levels of TGF-alpha and calcium-binding proteins were significantly increased (4.46- and 1.4-1.8-fold, respectively). Due to the diverse functions of these proteins, the results might contribute to understand the mechanisms involved in lung disorders induced by oil mist exposure.
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PMID:Proteomics analysis revealed changes in rat bronchoalveolar lavage fluid proteins associated with oil mist exposure. 1651 68

Calcium (Ca(2+)) signaling plays a major role in a wide range of physiological functions including control and regulation of cardiac and skeletal muscle performance and vascular tone. As all Ca(2+) signals require proteins to relay intracellular Ca(2+) oscillations downstream to different signaling networks, a specific toolkit of Ca(2+)-sensor proteins involving members of the EF-hand S100 Ca(2+) binding protein superfamily maintains the integrity of the Ca(2+) signaling in a variety of cardiac and vascular cells, transmitting the message with great precision and in a temporally and spatially coordinated manner. Indeed, the possibility that S100 proteins might contribute to heart and vascular diseases was first suggested by the discovery of distinctive patterns of S100 expression in healthy and diseased hearts and vasculature from humans and animal heart failure (HF) models. Based on more elaborate genetic studies in mice and strategies to manipulate S100 protein expression in human cardiac, skeletal muscle and vascular cells, it is now apparent that the integrity of distinct S100 protein isoforms in striated muscle and vascular cells such as S100A1, S100A4, S100A6, S100A8/A9 or S100B is a basic requirement for normal cardiovascular and muscular development and function; loss of integrity would naturally lead to profound deregulation of the implicated Ca(2+) signaling systems with detrimental consequences to cardiac, skeletal muscle, and vascular function. The brief debate and discussion here are confined by design to the biological actions and pathophysiological relevance of the EF-hand Ca(2+)-sensor protein S100A1 in the heart, vasculature and skeletal muscle with a particular focus on current translational therapeutic strategies. By virtue of its ability to modulate the activity of numerous key effector proteins that are essentially involved in the control of Ca(2+) and NO homeostasis in cardiac, skeletal muscle and vascular cells, S100A1 has been proven to play a critical role both in cardiac performance, blood pressure regulation and skeletal muscle function. Given that deregulated S100A1 expression in cardiomyocytes and endothelial cells has recently been linked to heart failure and hypertension, it is arguably a molecular target of considerable clinical interest as S100A1 targeted therapies have already been successfully investigated in preclinical translational studies.
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PMID:S100A1 in cardiovascular health and disease: closing the gap between basic science and clinical therapy. 1953 70

It is well established that calcium binding leads to conformational changes in S100 proteins. These conformational changes are thought to activate the protein and render a protein conformation that is capable of binding other proteins. The basic quaternary structural motif of S100 proteins is a homodimer, however there is little information if higher order non-covalent oligomers are also formed and whether these oligomers are of functional relevance. To this end we performed equilibrium analytical ultracentrifugation experiments for 16 S100 proteins (S100A1, S100A2, S100A3, S100A4, S100A5, S100A6, S100A7, S100A8, S100A9, S100A10, S100A11, S100A12, S100A13, S100B, S100P, and S100Z) under reducing conditions in the absence and presence of calcium ions. We show that the addition of calcium promotes the formation of tetrameric structures which could be further enhanced under in vivo conditions where there is an additional effect of molecular crowding.
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PMID:Modulation of quaternary structure of S100 proteins by calcium ions. 2062 10

The S100 gene family encode low molecular weight proteins implicated in cancer progression. In this study, we analyzed the expression of four S100 genes in one cohort of patients with breast cancer and 16 S100 genes in a second cohort. In both cohorts, the expression of S100A8 and S1009 mRNA level was elevated in high-grade compared to low-grade tumors and in estrogen receptor-negative compared to estrogen receptor-positive tumors. None of the S100 transcripts investigated were significantly associated with the presence of lymph node metastasis. Notably, multiple S100 genes, including S100A1, S100A2, S100A4, S100A6, S100A8, S100A9, S100A10, S100A11, and S100A14 were upregulated in basal-type breast cancers compared to non-basal types. Using Spearman's correlation analysis, several S100 transcripts correlated significantly with each other, the strongest correlation has been found between S100A8 and S100A9 (r = 0.889, P < 0.001, n = 295). Of the 16 S100 transcripts investigated, only S100A11 and S100A14 were significantly associated with patient outcome. Indeed, these two transcripts predicted outcome in the cohort of patients that did not receive systemic adjuvant therapy. Based on our findings, we conclude that the different S100 genes play varying roles in breast cancer progression. Specific S100 genes are potential targets for the treatment of basal-type breast cancers.
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PMID:The role of S100 genes in breast cancer progression. 2115 24

To investigate the effects of chronic exposure to arsenite on the gene expression profiles of mast cells, microarray analysis was performed on rat basophilic leukemia RBL-2H3 cells exposed to arsenite for 28 days. Upregulated genes include calcium-binding S100 proteins such as S100A9, S100A10, S100A6, and S100A13, and granzymes B and C. Among S100 proteins, S100A9 showed the highest expression (8.62-fold of untreated cells) after 4-weeks of exposure to arsenite. As S100A8 and S100A9 comprise a heterodimer called calprotectin, and are implicated in the development of atherosclerosis and cancer, mRNA levels of both S100A8 and S100A9 were analyzed. The results demonstrated that exposure of RBL-2H3 cells to arsenite for a few weeks induces marked increases in mRNA levels of S100A8 and S100A9.
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PMID:Chronic exposure to arsenite induces S100A8 and S100A9 expression in rat RBL-2H3 mast cells. 2129 53

EST analysis based on the megaclone-megasorting method was performed using leukocytes from the bottlenose dolphin (Tursiops truncatus) with or without LPS stimulation. A total of 849 upregulated and 384 downregulated EST clones were sequenced, annotated, and functionally classified. Ferritin heavy peptide I was the most abundant upregulated transcript, suggesting that LPS stimulation induced high production of reactive oxygen species, which were sequestered in ferritin. Among the immune factors, the transcripts coding for an IL-1Ra, homologs to bovine serum amyloid A3, and canine intercellular adhesion molecule-1 were highly expressed. Markedly downregulated transcripts of immune factors were those for homologs of calcium-binding proteins belonging to the S100 family, S100A12, S100A8, and S100A6. Time-course experiments on the expression of some immune factors including IL-1Ra suggested that these factors interact and control cetacean innate immunity.
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PMID:Lipopolysaccharide-induced innate immune factors in the bottlenose dolphin (Tursiops truncatus) detected in expression sequence tag analysis. 2183 Dec 3

This study tested the hypothesis that human eosinophils produce ligands for the receptor for advanced glycation end-products (RAGE), express RAGE and exhibit RAGE-mediated responses. In examining our microarray data, we identified the presence of RAGE and RAGE ligand (S100A4, S100A6, S100A8, S100A9, S100A11, S100P, HMGB1) transcripts. Expression of eosinophil RAGE mRNA was also compared with a known positive control and further assessed via bioinformatics and sequence analysis of RAGE cDNA. Positive and negative controls were used to identify RAGE, S100A8 and S100A9 protein in human primary eosinophils. Immunoblot assessment of eosinophils treated with cytokines (IL-5 or granulocyte macrophage colony-stimulating factor) indicated an up-regulation of S100A8 and S100A9 production, whereas co-treatment of eosinophils with a RAGE ligand and cytokines displayed a down-regulation in the levels of RAGE. Analysis of eosinophil-conditioned media revealed that eosinophils are capable of releasing RAGE, S100A8 and S100A9. To test the eosinophil response to RAGE activation, the most well-characterized RAGE ligand, S100B, was examined. Treatment of eosinophils with S100B resulted in RAGE-mediated PKC-delta phosphorylation, a 3-fold dose-dependent increase in cell survival and an increase in the level of cellular RAGE. Combined, these studies reveal eosinophil expression of RAGE, RAGE ligands and RAGE-mediated responses. The expression of eosinophil RAGE, soluble RAGE and RAGE ligands may be pivotal to the functions of eosinophils in various human diseases involving RAGE and S100 ligands.
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PMID:Human eosinophils express RAGE, produce RAGE ligands, exhibit PKC-delta phosphorylation and enhanced viability in response to the RAGE ligand, S100B. 2202 32

The vast diversity of S100 proteins has demonstrated a multitude of biological correlations with cell growth, cell differentiation and cell survival in numerous physiological and pathological conditions in all cells of the body. This review summarises some of the reported regulatory functions of S100 proteins (namely S100A1, S100A2, S100A4, S100A6, S100A7, S100A8/S100A9, S100A10, S100A11, S100A12, S100B and S100P) on cellular migration and invasion, established in both culture and animal model systems and the possible mechanisms that have been proposed to be responsible. These mechanisms involve intracellular events and components of the cytoskeletal organisation (actin/myosin filaments, intermediate filaments and microtubules) as well as extracellular signalling at different cell surface receptors (RAGE and integrins). Finally, we shall attempt to demonstrate how aberrant expression of the S100 proteins may lead to pathological events and human disorders and furthermore provide a rationale to possibly explain why the expression of some of the S100 proteins (mainly S100A4 and S100P) has led to conflicting results on motility, depending on the cells used.
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PMID:Joining S100 proteins and migration: for better or for worse, in sickness and in health. 2381 36


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