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)

Corpora amylacea (C.A.) also named polyglucosan bodies (P.B.) are one of the hallmarks of normal brain aging. Although their functions are not yet clear, C.A. increase in number in patients suffering from neurodegenerative diseases. C.A. contain 88% of hexoses and 4% of proteins. Most of the proteins in C.A. are aging or stress proteins such as heat shock proteins, ubiquitinated proteins and advanced glycation end products which are also proinflammatory products. Stimulated by the potential role played by some S100 proteins in the inflammatory process which may be triggered in C.A., we investigated, by immunohistochemistry, the presence of different S100 proteins (S100A1, S100A2, S100A3, S100A4, S100A5, S100A6, S100A8, S100A9, S100A12 and S100B) in C.A. from normal human brain. Among the ten S100 proteins analyzed, nine (S100A) were detected in C.A. Three S100 proteins (S100A8, S100A9, S100A12) which are highly expressed in activated macrophages and used as inflammatory markers were detected in C.A. S100A8 was, in addition, found in thick neuronal processes from the pons. One (S100B) could not be found in C.A. although it was highly expressed in astrocytes. In C.A., the staining intensity was estimated by computer-assisted microscopy and gave the following order: S100A1 congruent withS100A8 congruent with S100A9>S100A5> or =S100A4>S100A12>S100A6> S100A2=S100A3. The potential inflammatory role played by S100 proteins in C.A. is discussed.
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PMID:S100 proteins in Corpora amylacea from normal human brain. 1083 26

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

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

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

Inflammation, insoluble protein deposition and neuronal cell loss are important features of the Alzheimer's disease (AD) brain. S100B is associated with the neuropathological hallmarks of AD where it is thought to play a role in neuritic pathology. S100A8, S100A9 and S100A12 comprise a new group of inflammation-associated proteins that are constitutively expressed by neutrophils and inducible in numerous inflammatory cells. We investigated expression of S100B, S100A8, S100A9 and S100A12 in brain samples from sporadic and familial (PS-1) AD cases and controls using immunohistochemistry and Western blot analysis. S100B, S100A9 and S100A12, but not S100A8, were consistently associated with the neuropathological hallmarks of AD. Western blot analysis confirmed significant increases in soluble S100A9 in PS-1 AD compared to controls. S100A9 complexes that were resistant to reduction were also evident in brain extracts. A reactive component of a size consistent with hexameric S100A12 was seen in all cases. This study indicates a potential role for pro-inflammatory S100A9 and S100A12 in pathogenesis caused by inflammation and protein complex formation in AD.
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PMID:Inflammatory S100A9 and S100A12 proteins in Alzheimer's disease. 1625 91

The S100 proteins act as multifactional signaling factors that are involved in the regulation of diverse cellular processes. To explore the involvement of S100 genes in bladder cancers, S100 gene expressions were systematically evaluated at the RNA level by microarray and real-time PCR. Total RNAs were obtained from 4-hydroxybutyl(butyl)nitrosamine (OH-BBN)-induced mouse and rat bladder cancers, human bladder cancers and matched normal bladder urothelium. Microarray analysis was performed on mouse and rat bladder cancers; real-time PCR was performed in mouse, rat and human bladder cancers and their matched normal urothelium for confirmation. Microarray analysis revealed that 9 and 6 members of the S100 gene family were differentially expressed in mouse and rat bladder cancers, respectively. Thirteen members of the S100 gene family were confirmed by real-time PCR to be differentially expressed in human bladder cancers, with overexpression of S100A2, S100A3, S100A5, S100A7, S100A8, S100A9, S100A14, S100A15, S100A16 and S100P, and underexpression of S100A1, S100A4 and S100B. S100A1, S10OA3, S100A8, S10A9, S100A14, S100A15 and S100A16 showed similar patterns of differential expression in bladder cancers from mouse, rat and human. To our knowledge this is the first report of systematic evaluation of S100 gene expressions in bladder cancers. Our results indicate that differential expression of S100 gene family members is characteristic of bladder cancers and these genes may play important roles in bladder tumorigenesis and progression.
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PMID:Expression of S100 protein family members in the pathogenesis of bladder tumors. 1797 44

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

S100B and S100A10 are dimeric, EF-hand proteins. S100B undergoes a calcium-dependent conformational change allowing it to interact with a short contiguous sequence from the actin-capping protein CapZ (TRTK12). S100A10 does not bind calcium but is able to recruit the N-terminus of annexin A2 important for membrane fusion events, and to form larger multiprotein complexes such as that with the cation channel proteins TRPV5/6. In this work, we have designed, expressed, purified, and characterized two S100-target peptide hybrid proteins comprised of S100A10 and S100B linked in tandem to annexin A2 (residues 1-15) and CapZ (TRTK12), respectively. Different protease cleavage sites (tobacco etch virus, PreScission) were incorporated into the linkers of the hybrid proteins. In situ proteolytic cleavage monitored by (1)H-(15)N HSQC spectra showed the linker did not perturb the structures of the S100A10-annexin A2 or S100B-TRTK12 complexes. Furthermore, the analysis of the chemical shift assignments ((1)H, (15)N, and (13)C) showed that residues T102-S108 of annexin A2 formed a well-defined alpha-helix in the S100A10 hybrid while the TRTK12 region was unstructured at the N-terminus with a single turn of alpha-helix from D108-K111 in the S100B hybrid protein. The two S100 hybrid proteins provide a simple yet extremely efficient method for obtaining high yields of intact S100 target peptides. Since cleavage of the S100 hybrid protein is not necessary for structural characterization, this approach may be useful as a scaffold for larger S100 complexes.
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PMID:Design of high-affinity S100-target hybrid proteins. 1982 97

The accumulation of advanced glycation end products is thought to be a key factor in the initiation and progression of diabetic nephropathy. Here we determined whether the size of the ligands for the receptor for advanced glycation end products (RAGEs) that were present in the serum of patients with type 2 diabetes modulates their pathogenic potential. Serum was collected from control subjects and patients with type 2 diabetes with varying degrees of renal disease (normo-, micro-, or macroalbuminuria). The titers of the RAGE ligands N-carboxymethyllysine (CML), S100A, S100B, and high-mobility group box 1 (HMGB1) were measured by enzyme-linked immunosorbent assay in serum as well as in pooled size-fractionated serum. We also measured cellular binding of serum fractions to mesangial cells transfected with RAGE and examined the downstream signaling pathways. Circulating CML was increased in patients with type 2 diabetes, whereas HMGB1 was decreased. S100A8, S100BA9, and soluble RAGE were unchanged. The high-molecular-weight (over 50 kDa) serum fraction contained the greatest proportion of RAGE ligands, with all immunoreactivity and cellular binding observed only with serum fractions over 30 kDa. High-molecular-weight serum from macroalbuminuric patients showed greater RAGE binding capacity, modulation of cell-surface RAGE expression, increased phospho-protein kinase C-alpha, and p65 nuclear factor kappaB DNA-binding activity, which were competitively inhibited by soluble RAGE or CML neutralizing antibodies. These data show that ligands that activate RAGE present in the circulation of patients with type 2 diabetes and nephropathy are predominantly of high molecular weight.
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PMID:Circulating high-molecular-weight RAGE ligands activate pathways implicated in the development of diabetic nephropathy. 2063 34

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


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