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Stimulation of excitatory amino acid release from adult mouse brain glia subcellular particles by high mobility group box 1 protein
Author(s) -
Pedrazzi Marco,
Raiteri Luca,
Bonanno Giambattista,
Patrone Mauro,
Ledda Sabina,
Passalacqua Mario,
Milanese Marco,
Melloni Edon,
Raiteri Maurizio,
Pontremoli Sandro,
Sparatore Bianca
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04120.x
Subject(s) - glutamate receptor , hmgb1 , glutamatergic , synaptosome , glutamate aspartate transporter , biology , cerebellum , neurotransmitter , stimulation , high mobility group , astrocyte , microbiology and biotechnology , biochemistry , metabotropic glutamate receptor , neuroscience , central nervous system , receptor , gene
The multifunctional protein high mobility group box 1 (HMGB1) is expressed in hippocampus and cerebellum of adult mouse brain. Our aim was to determine whether HMGB1 affects glutamatergic transmission by monitoring neurotransmitter release from glial (gliosomes) and neuronal (synaptosomes) re‐sealed subcellular particles isolated from cerebellum and hippocampus. HMGB1 induced release of the glutamate analogue [ 3 H] d ‐aspartate form gliosomes in a concentration‐dependent manner, whereas nerve terminals were insensitive to the protein. The HMGB1‐evoked release of [ 3 H] d ‐aspartate was independent of modifications of cytosolic Ca 2+ , but it was blocked by dl ‐threo‐β‐benzyloxyaspartate ( dl ‐TBOA), an inhibitor of glutamate transporters. HMGB1 also stimulated the release of endogenous glutamate in a Ca 2+ ‐independent and dl ‐TBOA‐sensitive manner. These findings suggest the involvement of carrier‐mediated release. Moreover, dihydrokainic acid, a selective inhibitor of glutamate transporter 1 (GLT1), does not block the effect of HMGB1, indicating a role for the glial glutamate‐aspartate transporter (GLAST) subtype in this response. We also demonstrate that HMGB1/glial particles association is promoted by Ca 2+ . Furthermore, although HMGB1 can physically interact with GLAST and the receptor for advanced glycation end products (RAGE), only its binding with RAGE is promoted by Ca 2+ . These results suggest that the HMGB1 cytokine could act as a modulator of glutamate homeostasis in adult mammal brain.