Proteins of the Brain Extracellular Fluid: Evidence for Release of S‐100 Protein

Shashoua, Victor E.; Hesse, Gary W.; Moore, Blake W.

doi:10.1111/j.1471-4159.1984.tb12739.x

Cited by 175 publications

(68 citation statements)

References 25 publications

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“…We could show that about 66% of S100A6 content in glioblastoma cells was released within 20 min following an increase of intracellular Ca 2ϩ . In addition, the S100 proteins represent about 0.2% of the soluble proteins present in the extracellular space of the rat brain, a value 3-6-fold higher than the S100 protein levels in the cytoplasmic fraction (60). Altogether these observations make it very plausible that S100B and S100A6 occur at high levels in the brain where they could thus play the role of mediators of brain cell communication like glutamate, Ca 2ϩ , or acetylcholine.…”

Section: Discussionmentioning

confidence: 73%

S100B and S100A6 Differentially Modulate Cell Survival by Interacting with Distinct RAGE (Receptor for Advanced Glycation End Products) Immunoglobulin Domains

Leclerc

Fritz

Weibel

et al. 2007

Journal of Biological Chemistry

237

207

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S100 proteins are EF-hand calcium-binding proteins with various intracellular functions including cell proliferation, differentiation, migration, and apoptosis. Some S100 proteins are also secreted and exert extracellular paracrine and autocrine functions. Experimental results suggest that the receptor for advanced glycation end products (RAGE) plays important roles in mediating S100 protein-induced cellular signaling. Here we compared the interaction of two S100 proteins, S100B and S100A6, with RAGE by in vitro assay and in culture of human SH-SY5Y neuroblastoma cells. Our in vitro binding data showed that S100B and S100A6, although structurally very similar, interact with different RAGE extracellular domains. Our cell assay data demonstrated that S100B and S100A6 differentially modulate cell survival. At micromolar concentration, S100B increased cellular proliferation, whereas at the same concentration, S100A6 triggered apoptosis. Although both S100 proteins induced the formation of reactive oxygen species, S100B recruited phosphatidylinositol 3-kinase/AKT and NF-B, whereas S100A6 activated JNK. More importantly, we showed that S100B and S100A6 modulate cell survival in a RAGE-dependent manner; S100B specifically interacted with the RAGE V and C 1 domains and S100A6 specifically interacted with the C 1 and C 2 RAGE domains. Altogether these results highlight the complexity of S100/RAGE cellular signaling.

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Section: Discussionmentioning

confidence: 73%

S100B and S100A6 Differentially Modulate Cell Survival by Interacting with Distinct RAGE (Receptor for Advanced Glycation End Products) Immunoglobulin Domains

Leclerc

Fritz

Weibel

et al. 2007

Journal of Biological Chemistry

237

207

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“…The heterodimer (αβ) and homodimer (ββ, called S-100B) are present in high concentrations in astrocytes and Schwann cells (15). Small quantities of S-100B are also located in the cerebrospinal fluid at concentrations of 1.43 ± 0.49 μg/L (17) and in the brain interstitial fluid as well (21). The S-100B protein has a half-life in the serum of 2 hours (22).…”

Section: Discussionmentioning

confidence: 99%

Failure of Intraoperative Jugular Bulb S-100B and Neuron-Specific Enolase Sampling to Predict Cognitive Injury after Carotid Endarterectomy

et al. 2003

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OBJECTIVE-Cognitive decline occurs in 25% of patients after carotid endarterectomy (CEA). Elevated serum concentrations of S-100B and neuron-specific enolase (NSE) occur after stroke, and serum S-100B levels at 24 hours are associated with clinical outcome after both stroke and CEA. We hypothesized that we could detect acute elevations in serum levels of these markers obtained intraoperatively from the jugular bulb (JB) and that these elevations would predict cognitive dysfunction postoperatively as measured by neuropsychometric test performance.METHODS-Forty-three patients scheduled for elective CEA were assessed with a battery of neuropsychometric tests before and 1 day after surgery. Before the carotid artery was clamped, a 6-French Fogarty catheter was inserted into the facial vein and threaded 6 cm rostrally into the JB. Serum samples were withdrawn from this catheter and simultaneously from a radial arterial catheter (A-line) at three time points: before clamping, 15 minutes into clamping, and after unclamping the carotid artery. Concentrations between groups were compared by analysis of variance and paired t tests.RESULTS-Total deficit scores were significantly worse in 13 (30%) of the 43 patients 1 day after surgery. There was a trend toward elevations in JB concentrations of S-100B relative to A-line levels 15 minutes after cross-clamping (11% elevation, P = 0.079, paired t test). In addition, 15 minutes NIH Public Access Author ManuscriptNeurosurgery. Author manuscript; available in PMC 2009 March 31. Published in final edited form as:Neurosurgery. 2003 December ; 53(6): 1243-1250. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript after clamping of the carotid artery, levels of S-100B from the JB were significantly elevated Robert J. Dempsey Madison, Wisconsin 1. Connolly ES Jr, Winfree CJ, Rampersad A, Sharma R, Mack WJ, Mocco J, Solomon RA, Todd G, Quest DO, Stern Y, Heyer EJ: Serum S100B protein levels are correlated with subclinical neurocognitive declines after carotid endarterectomy. Neurosurgery 49: [1076][1077][1078][1079][1080][1081][1082][1083] 2001. The authors tested the hypothesis that changes in serum S-100B and NSE during endarterectomy may predict post-operative cognitive dysfunction. This hypothesis is based on literature linking these two proteins (which are normally found in the brain extracellular space) to brain damage; several reports have shown that both serum markers were elevated after head injury, ischemia, cardiac arrest, etc. The fact that S-100B (but not NSE) is also elevated after a variety of conditions not associated with any "brain damage" (e.g., running a marathon, mild depression) led our laboratory to formulate the hypothesis that S-100B is a marker of BBB leakage, even in the absence of neuronal damage. This was confirmed in patients with primary central nervous system lymphoma who were undergoing iatrogenic BBB disruption with mannitol. After administration of mannitol, there was an immediate increase in S-100B serum levels, which re...

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“…This is consistent with the observations that members of the S100 gene family lacking a basic residue-rich domain at their carboxyl terminus are released into the extracellular compartment following expression in mammalian cells (17,18,21) and may imply that the carboxyl-terminal basic residue-rich domain in S100A13 functions to associate with target proteins, while the remainder of the S100A13 may be involved in penetration through the lipid bilayer. Indeed, S100B and S100A10 do not contain a basic residue-rich domain, yet S100B is released by glial cells (55,56), and S100A10 has been reported not only to associate with plasminogen in the extracellular compartment but is able to stimulate tissue-dependent plasminogen activation either alone or as a complex with Anx2 (57). These and other studies (58,59) have implicated the function of S100, Anx2, and phosphatidylserine as key mediators of the extrinsic coagulation and fibrinolytic systems on the surface of the endothelial cell (57)(58)(59).…”

Section: A S100a13 Mutant Lacking the Basic Residue-rich Domain Functmentioning

confidence: 99%

S100A13 Participates in the Release of Fibroblast Growth Factor 1 in Response to Heat Shock in Vitro

Landriscina¹,

Soldi

Bagalá

et al. 2001

Journal of Biological Chemistry

219

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S100A13, a member of the S100 gene family of Ca 2؉ -binding proteins has been previously characterized as a component of a brain-derived heparin-binding multiprotein aggregate/complex containing fibroblast growth factor 1 (FGF1). We report that while expression of S100A13 in NIH 3T3 cells results in the constitutive release of S100A13 into the extracellular compartment at 37°C, co-expression of S100A13 with FGF1 represses the constitutive release of S100A13 and enables NIH 3T3 cells to release S100A13 in response to temperature stress. S100A13 release in response to stress occurs with kinetics similar to that observed for the stress-induced release of FGF1, but S100A13 expression is able to reverse the sensitivity of FGF1 release to inhibitors of transcription and translation. The release of FGF1 and S100A13 in response to heat shock results in the solubility of FGF1 at 100% (w/v) ammonium sulfate saturation, and the expression of a S100A13 deletion mutant lacking its novel basic residue-rich domain acts as a dominant negative effector of FGF1 release in vitro. Surprisingly, the expression of S100A13 also results in the stress-induced release of a Cys-free FGF1 mutant, which is normally not released from NIH 3T3 cells in response to heat shock. These data suggest that S100A13 may be a component of the pathway for the release of the signal peptide-less polypeptide, FGF1, and may involve a role for S100A13 in the formation of a noncovalent FGF1 homodimer. FGF11 and FGF2 are the prototype members of a large family of heparin-binding growth factor genes that regulate numerous biological processes such as neurogenesis, mesoderm formation, and angiogenesis (1, 2). FGF1 and FGF2 lack a classical signal peptide sequence that provides access to the conventional endoplasmic reticulum (ER)-Golgi secretion pathway, a characteristic that led to the hypothesis that the release of these polypeptides may proceed through novel release/export pathways (2). Our laboratory previously demonstrated that FGF1, but not FGF2, is released as a latent homodimer by a transcription-and translation-dependent mechanism in response to a variety of cellular stresses including heat shock (3), hypoxia (4), and serum starvation (5). Conversely, the disruption of communication between the ER and Golgi apparatus by brefeldin A does not prevent the release of FGF1 from NIH 3T3 cells, confirming that FGF1 release may occur through a nonconventional pathway (6).FGF1 is released in vitro as a reducing agent-and denaturant-sensitive complex, which contains the p40 extravesicular domain of the Ca 2ϩ -binding protein, p65 synaptotagmin (Syt)1 (7). The release of FGF1 in response to stress is dependent on Syt1 expression, since the expression of either a deletion mutant lacking 95 amino acids from the extravesicular portion of Syt1 or an antisense-Syt1 gene is able to repress FGF1 release in NIH 3T3 cells (7,8). In addition, FGF1 purified from ovine brain as a high molecular weight aggregate exists as a component of a noncovalent heparin-binding complex wit...

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Proteins of the Brain Extracellular Fluid: Evidence for Release of S‐100 Protein

Cited by 175 publications

References 25 publications

S100B and S100A6 Differentially Modulate Cell Survival by Interacting with Distinct RAGE (Receptor for Advanced Glycation End Products) Immunoglobulin Domains

S100B and S100A6 Differentially Modulate Cell Survival by Interacting with Distinct RAGE (Receptor for Advanced Glycation End Products) Immunoglobulin Domains

Failure of Intraoperative Jugular Bulb S-100B and Neuron-Specific Enolase Sampling to Predict Cognitive Injury after Carotid Endarterectomy

S100A13 Participates in the Release of Fibroblast Growth Factor 1 in Response to Heat Shock in Vitro

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