Neurite extension and neuronal survival activities of recombinant S100 beta proteins that differ in the content and position of cysteine residues.

Winningham-Major, F; Staecker, Jeffrey L.; Barger, Steven W.; Coats, Steven; Eldik, Linda J. Van

doi:10.1083/jcb.109.6.3063

Cited by 261 publications

(151 citation statements)

References 45 publications

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“…In this context, S100B dimers linked together by disulfide bonds induce neurite outgrowth, but dimers without disulfide bonds can induce an inflammatory response in glial cells (49,50). Furthermore, noncovalent tetramers of S100B found in human brain extracts appear to induce RAGE multimerization (51).…”

Section: Discussionmentioning

confidence: 99%

Transamidation by Transglutaminase 2 Transforms S100A11 Calgranulin into a Procatabolic Cytokine for Chondrocytes

Cecil

Terkeltaub

2008

The Journal of Immunology

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In osteoarthritis (OA), low-grade joint inflammation promotes altered chondrocyte differentiation and cartilage catabolism. S100/calgranulins share conserved calcium-binding EF-hand domains, associate noncovalently as homodimers and heterodimers, and are secreted and bind receptor for advanced glycation end products (RAGE). Chondrocyte RAGE expression and S100A11 release are stimulated by IL-1β in vitro and increase in OA cartilage in situ. Exogenous S100A11 stimulates chondrocyte hypertrophic differentiation. Moreover, S100A11 is covalently cross-linked by transamidation catalyzed by transglutaminase 2 (TG2), itself an inflammation-regulated and redox stress-inducible mediator of chondrocyte hypertrophic differentiation. In this study, we researched mouse femoral head articular cartilage explants and knee chondrocytes, and a soluble recombinant double point mutant (K3R/Q102N) of S100A11 TG2 transamidation substrate sites. Both TG2 and RAGE knockout cartilage explants retained IL-1β responsiveness. The K3R/Q102N mutant of S100A11 retained the capacity to bind to RAGE and chondrocytes but lost the capacity to signal via the p38 MAPK pathway or induce chondrocyte hypertrophy and glycosaminoglycans release. S100A11 failed to induce hypertrophy, glycosaminoglycan release, and appearance of the aggrecanase neoepitope NITEGE in both RAGE and TG2 knockout cartilages. We conclude that transamidation by TG2 transforms S100A11 into a covalently bonded homodimer that acquires the capacity to signal through the p38 MAPK pathway, accelerate chondrocyte hypertrophy and matrix catabolism, and thereby couple inflammation with chondrocyte activation to potentially promote OA progression.

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Section: Discussionmentioning

confidence: 99%

Transamidation by Transglutaminase 2 Transforms S100A11 Calgranulin into a Procatabolic Cytokine for Chondrocytes

Cecil

Terkeltaub

2008

The Journal of Immunology

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“…DISCUSSION S100B belongs to the S100/calmodulin/troponin C superfamily of proteins that function as calcium-modulated proteins and exert their effects on the CNS in a concentration-and calciumdependent manner. 24 Extracellular S100B promotes neurite extension outgrowth and enhances cell maintenance in cultures of embryonic chick cerebral cortex neurons 25 and stimulates proliferation of primary rat astrocytes. 26 Increased intracellular calcium by S100B protein has been reported to decrease neuronal cell death and mitochondrial dysfunction in rat hippocampal neurons may provide neuroprotection for CNS neurons at nanomolar concentrations.…”

Section: S100b Does Not Influence Key Microglial Activation Markers Imentioning

confidence: 99%

S100B Inhibition Reduces Behavioral and Pathologic Changes in Experimental Traumatic Brain Injury

Kabadi

Stoica

Zimmer

et al. 2015

J Cereb Blood Flow Metab

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Neuroinflammation following traumatic brain injury (TBI) is increasingly recognized to contribute to chronic tissue loss and neurologic dysfunction. Circulating levels of S100B increase after TBI and have been used as a biomarker. S100B is produced by activated astrocytes and can promote microglial activation; signaling by S100B through interaction with the multiligand advanced glycation end product-specific receptor (AGER) has been implicated in brain injury and microglial activation during chronic neurodegeneration. We examined the effects of S100B inhibition in a controlled cortical impact model, using S100B knockout mice or administration of neutralizing S100B antibody. Both interventions significantly reduced TBI-induced lesion volume, improved retention memory function, and attenuated microglial activation. The neutralizing antibody also significantly reduced sensorimotor deficits and improved neuronal survival in the cortex. However, S100B did not alter microglial activation in BV2 cells or primary microglial cultures stimulated by lipopolysaccharide or interferon gamma. Further, proximity ligation assays did not support direct interaction in the brain between S100B and AGER following TBI. Future studies are needed to elucidate specific pathways underlying S100B-mediated neuroinflammatory actions after TBI. Our results strongly implicate S100B in TBI-induced neuroinflammation, cell loss, and neurologic dysfunction, thereby indicating that it is a potential therapeutic target for TBI.

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“…S100B protein is released by astrocytes into the extracellular space (27,28) and could directly modulate synaptic mechanisms. To test this possibility, we perfused a disulfide-bonded dimer of S100B (10,29) throughout the recording period at a concentration of 1 g͞ml, which is equivalent to the concentration in extracellular fluid of rat hippocampus (27). Exogenous S100B reversed the level of LTP in the mutant mouse slices to those of the wild-type mouse slices, whereas the same treatment did not affect the level of LTP in wild-type mouse slices (Fig.…”

Section: S100b-null Mice Developedmentioning

confidence: 99%

Glial protein S100B modulates long-term neuronal synaptic plasticity

Nishiyama

Knöpfel

Endo

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

246

168

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Glial cells are traditionally regarded as elements for structural support and ionic homeostasis, but have recently attracted attention as putative integral elements of the machinery involved in synaptic transmission and plasticity. Here, we demonstrate that calcium-binding protein S100B, which is synthesized in considerable amounts in astrocytes (a major glial cell subtype), modulates long-term synaptic plasticity. Mutant mice devoid of S100B developed normally and had no detectable abnormalities in the cytoarchitecture of the brain. These mutant mice, however, had strengthened synaptic plasticity as identified by enhanced longterm potentiation (LTP) in the hippocampal CA1 region. Perfusion of hippocampal slices with recombinant S100B proteins reversed the levels of LTP in the mutant slices to those of the wild-type slices, indicating that S100B might act extracellularly. In addition to enhanced LTP, mutant mice had enhanced spatial memory in the Morris water maze test and enhanced fear memory in the contextual fear conditioning. The results indicate that S100B is a glial modulator of neuronal synaptic plasticity and strengthen the notion that glial-neuronal interaction is important for information processing in the brain.S everal lines of evidence suggest that glial cells play an active role in excitatory neurotransmission in the central nervous system (1, 2). For instance, astrocytes can release glutamate in response to physiological increases in their intracellular calcium concentration, and then evoke substantial glutamatergic currents in neighboring neurons (3). Oligodendrocyte precursor cells directly receive glutamatergic inputs from hippocampal pyramidal neurons (4). These findings, together with earlier studies showing that glial cells express many types of neurotransmitter receptors and respond to neurotransmitter by generating slowly propagating calcium waves (5), suggest that glialneuronal reciprocal signaling may play a role in synaptic plasticity and eventually in information processing in the brain. Indeed, this notion has been supported by the findings that the mice devoid of glial fibrillary acidic protein (GFAP: an intermediate filament specific to astrocytes) showed enhanced longterm potentiation (LTP) in the hippocampal CA1 region and decreased long-term depression in the cerebellum associated with impaired eye-blink conditioning (6, 7). However, the molecular mechanism underlying glial-neuronal interactions is poorly understood.One of the candidates that might be involved in glia-to-neuron signaling is the calcium-binding protein S100B. S100B is a member of the S100 family of proteins containing two EF-handtype calcium-binding domains (8). The highest level of expression of the S100B protein is in the brain and is found primarily in the cytoplasm of astrocytes (9). Results of in vitro studies suggest a variety of intracellular functions of S100B, including cell growth, cell structure, energy metabolism, and calcium homeostasis (8). S100B is secreted from astrocytes, suggesting that it might ...

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Neurite extension and neuronal survival activities of recombinant S100 beta proteins that differ in the content and position of cysteine residues.

Cited by 261 publications

References 45 publications

Transamidation by Transglutaminase 2 Transforms S100A11 Calgranulin into a Procatabolic Cytokine for Chondrocytes

Transamidation by Transglutaminase 2 Transforms S100A11 Calgranulin into a Procatabolic Cytokine for Chondrocytes

S100B Inhibition Reduces Behavioral and Pathologic Changes in Experimental Traumatic Brain Injury

Glial protein S100B modulates long-term neuronal synaptic plasticity

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