Ammonia-induced alteration in S100B secretion in astrocytes is not reverted by creatine addition.
Hyperammonemia is a major element in the pathogenesis of hepatic encephalopathy (HE) and ammonia neurotoxicity involves an effect on the glutamatergic neurotransmitter system. Astrocytes are intimately related to glutamatergic neurotransmission and, in fact, many specific glial alterations have been reported as a result of ammonia exposure. S100B protein, particularly extracellular S100B, is used as a parameter of glial activation or commitment in several situations of brain injury. However, there is little information about this protein in ammonia toxicity and none about its secretion in astrocytes under ammonia exposure. In this study, we investigated S100B secretion in rat cortical astrocytes acutely exposed to ammonia, as well astrocyte morphology, glial fibrillary acidic protein (GFAP) content and glutamine synthetase (GS) activity. Moreover, we studied a possible effect of creatine on these glial parameters, since this compound has a putative role against ammonia toxicity in cell cultures. We found an increase in S100B secretion by astrocytes exposed to ammonia for 24h, accompanied by a decrease in GFAP content and GS activity. Since elevated and persistent extracellular S100B plays a toxic effect on neural cells, altered extracellular content of S100B induced by ammonia could contribute to the brain impairment observed in HE. Creatine addition did not prevent this increment in S100B secretion, but was able to prevent the decrease in GFAP content and GS activity induced by ammonia exposure.
Leite
Marina Concli
MC
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Brolese
Giovana
G
de Almeida
Lucia Maria Vieira
LM
Piñero
Cristopher Celintano
CC
Gottfried
Carmem
C
Gonçalves
Carlos-Alberto
CA
D000641:Ammonia / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism*; D002478:Cells, Cultured; D003401:Creatine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D009414:Nerve Growth Factors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism*
D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579158:S100b protein, rat; D000641:Ammonia; D003401:Creatine