High glutamate decreases S100B secretion by a mechanism dependent on the glutamate transporter.
Several molecules have been shown to be involved in glial-neuronal communication, including S100B, an astrocyte-derived neurotrophic cytokine. Extracellular S100B protects hippocampal neurons from excitotoxic damage, whilst toxic levels of glutamate to neurons have been shown to reduce S100B secretion in astrocytes and brain slices, by an unknown mechanism. Here, we investigate which mechanisms are possibly involved in this effect in primary cultures of hippocampal astrocytes using glutamate agonists and glutamate uptake inhibitors. DCG-IV, an agonist of group II metabotropic glutamate receptors, caused a smaller decrease in S100B secretion when compared to 1 mM glutamate. D: -aspartate partially reverted the glutamate effect on S100B release and two other inhibitors, PDC and DIDS, reverted it completely. These findings suggest that S100B secretion is inversely coupled to glutamate uptake. Decrease in S100B secretion may be considered as direct excitotoxic damage, but a beneficial mechanism effect cannot be ruled out, because S100B elevation could cause an additional cell death.
Tramontina
Francine
F
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Leite
Marina C
MC
Gonçalves
Daniela
D
Tramontina
Ana Carolina
AC
Souza
Daniela F
DF
Frizzo
Juliana K
JK
Nardin
Patrícia
P
Gottfried
Carmem
C
Wofchuk
Susana T
ST
Gonçalves
Carlos-Alberto
CA
D027322:Amino Acid Transport System X-AG / Q000502:physiology*; D000818:Animals; D016895:Culture Media, Serum-Free; D018698:Glutamic Acid / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D009414:Nerve Growth Factors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism*
D027322:Amino Acid Transport System X-AG; D016895:Culture Media, Serum-Free; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579158:S100b protein, rat; D018698:Glutamic Acid