Abstract
The multifunctional protein high-mobility group box 1 (HMGB1) is expressed in restricted areas of adult brain where it can act as a proinflammatory cytokine. We report here that HMGB1 affects CNS transmission by inducing glutamatergic release from glial (gliosomes) but not neuronal (synaptosomes) resealed subcellular particles isolated from mouse cerebellum and hippocampus. Confocal microscopy showed that gliosomes are enriched with glia-specific proteins such as GFAP and S-100, but not with neuronal proteins such as PSD-95, MAP-2, and β-tubulin III. Furthermore, gliosomes exhibit labeling neither for integrin-αM nor for myelin basic protein, specific for microglia and oligodendrocytes, respectively. The gliosomal fraction contains proteins of the exocytotic machinery coexisting with GFAP. Consistent with ultrastructural analysis, several ∼30-nm nonclustered vesicles are present in the gliosome cytoplasm. Finally, gliosomes represent functional organelles that actively export glutamate when subjected to releasing stimuli, such as ionomycin or ATP, by mechanisms involving extracellular Ca2+ and Ca2+ release from intracellular stores. HMGB1-induced release of the stable glutamate analogue [3H]d-aspartate and endogenous glutamate form gliosomes, whereas nerve terminals were insensitive to the protein. The HMGB1-evoked release of glutamate was independent on modifications of cytosolic Ca2+ concentration, but it was blocked by dl-threo-β-benzyloxyaspartate, suggesting the involvement of transporter-mediated release mechanisms. Moreover, dihydrokainic acid, a selective inhibitor of glutamate transporter 1 does not block the HMGB1 effect, indicating a role for the glial glutamate-aspartate transporter (GLAST) subtype in this response. HMGB1 bind to gliosomes but not to synaptosomes and can physically interact with GLAST and receptor for advanced glycation end products (RAGE). Taken together, these results suggest that the HMGB1 cytokine could act as a modulator of glutamate homeostasis in adult mammalian brain.
| Original language | English |
|---|---|
| Pages (from-to) | 73-93 |
| Number of pages | 21 |
| Journal | International Review of Neurobiology |
| Volume | 82 |
| DOIs | |
| Publication status | Published - 2007 |
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ASJC Scopus subject areas
- Neuroscience(all)
- Neuropsychology and Physiological Psychology
- Physiology
Cite this
The High-Mobility Group Box 1 Cytokine Induces Transporter-Mediated Release of Glutamate from Glial Subcellular Particles (Gliosomes) Prepared from in Situ-Matured Astrocytes. / Bonanno, Giambattista; Raiteri, Luca; Milanese, Marco; Zappettini, Simona; Melloni, Edon; Pedrazzi, Marco; Passalacqua, Mario; Tacchetti, Carlo; Usai, Cesare; Sparatore, Bianca.
In: International Review of Neurobiology, Vol. 82, 2007, p. 73-93.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The High-Mobility Group Box 1 Cytokine Induces Transporter-Mediated Release of Glutamate from Glial Subcellular Particles (Gliosomes) Prepared from in Situ-Matured Astrocytes
AU - Bonanno, Giambattista
AU - Raiteri, Luca
AU - Milanese, Marco
AU - Zappettini, Simona
AU - Melloni, Edon
AU - Pedrazzi, Marco
AU - Passalacqua, Mario
AU - Tacchetti, Carlo
AU - Usai, Cesare
AU - Sparatore, Bianca
PY - 2007
Y1 - 2007
N2 - The multifunctional protein high-mobility group box 1 (HMGB1) is expressed in restricted areas of adult brain where it can act as a proinflammatory cytokine. We report here that HMGB1 affects CNS transmission by inducing glutamatergic release from glial (gliosomes) but not neuronal (synaptosomes) resealed subcellular particles isolated from mouse cerebellum and hippocampus. Confocal microscopy showed that gliosomes are enriched with glia-specific proteins such as GFAP and S-100, but not with neuronal proteins such as PSD-95, MAP-2, and β-tubulin III. Furthermore, gliosomes exhibit labeling neither for integrin-αM nor for myelin basic protein, specific for microglia and oligodendrocytes, respectively. The gliosomal fraction contains proteins of the exocytotic machinery coexisting with GFAP. Consistent with ultrastructural analysis, several ∼30-nm nonclustered vesicles are present in the gliosome cytoplasm. Finally, gliosomes represent functional organelles that actively export glutamate when subjected to releasing stimuli, such as ionomycin or ATP, by mechanisms involving extracellular Ca2+ and Ca2+ release from intracellular stores. HMGB1-induced release of the stable glutamate analogue [3H]d-aspartate and endogenous glutamate form gliosomes, whereas nerve terminals were insensitive to the protein. The HMGB1-evoked release of glutamate was independent on modifications of cytosolic Ca2+ concentration, but it was blocked by dl-threo-β-benzyloxyaspartate, suggesting the involvement of transporter-mediated release mechanisms. Moreover, dihydrokainic acid, a selective inhibitor of glutamate transporter 1 does not block the HMGB1 effect, indicating a role for the glial glutamate-aspartate transporter (GLAST) subtype in this response. HMGB1 bind to gliosomes but not to synaptosomes and can physically interact with GLAST and receptor for advanced glycation end products (RAGE). Taken together, these results suggest that the HMGB1 cytokine could act as a modulator of glutamate homeostasis in adult mammalian brain.
AB - The multifunctional protein high-mobility group box 1 (HMGB1) is expressed in restricted areas of adult brain where it can act as a proinflammatory cytokine. We report here that HMGB1 affects CNS transmission by inducing glutamatergic release from glial (gliosomes) but not neuronal (synaptosomes) resealed subcellular particles isolated from mouse cerebellum and hippocampus. Confocal microscopy showed that gliosomes are enriched with glia-specific proteins such as GFAP and S-100, but not with neuronal proteins such as PSD-95, MAP-2, and β-tubulin III. Furthermore, gliosomes exhibit labeling neither for integrin-αM nor for myelin basic protein, specific for microglia and oligodendrocytes, respectively. The gliosomal fraction contains proteins of the exocytotic machinery coexisting with GFAP. Consistent with ultrastructural analysis, several ∼30-nm nonclustered vesicles are present in the gliosome cytoplasm. Finally, gliosomes represent functional organelles that actively export glutamate when subjected to releasing stimuli, such as ionomycin or ATP, by mechanisms involving extracellular Ca2+ and Ca2+ release from intracellular stores. HMGB1-induced release of the stable glutamate analogue [3H]d-aspartate and endogenous glutamate form gliosomes, whereas nerve terminals were insensitive to the protein. The HMGB1-evoked release of glutamate was independent on modifications of cytosolic Ca2+ concentration, but it was blocked by dl-threo-β-benzyloxyaspartate, suggesting the involvement of transporter-mediated release mechanisms. Moreover, dihydrokainic acid, a selective inhibitor of glutamate transporter 1 does not block the HMGB1 effect, indicating a role for the glial glutamate-aspartate transporter (GLAST) subtype in this response. HMGB1 bind to gliosomes but not to synaptosomes and can physically interact with GLAST and receptor for advanced glycation end products (RAGE). Taken together, these results suggest that the HMGB1 cytokine could act as a modulator of glutamate homeostasis in adult mammalian brain.
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UR - http://www.scopus.com/inward/citedby.url?scp=34547353633&partnerID=8YFLogxK
U2 - 10.1016/S0074-7742(07)82004-6
DO - 10.1016/S0074-7742(07)82004-6
M3 - Article
C2 - 17678956
AN - SCOPUS:34547353633
VL - 82
SP - 73
EP - 93
JO - International Review of Neurobiology
JF - International Review of Neurobiology
SN - 0074-7742
ER -