PMID- 25777939 OWN - NLM STAT- MEDLINE DCOM- 20151230 LR - 20200106 IS - 1873-474X (Electronic) IS - 0736-5748 (Linking) VI - 42 DP - 2015 May TI - In vitro evidence that sulfite impairs glutamatergic neurotransmission and inhibits glutathione metabolism-related enzymes in rat cerebral cortex. PG - 68-75 LID - S0736-5748(15)00033-7 [pii] LID - 10.1016/j.ijdevneu.2015.03.005 [doi] AB - Sulfite oxidase (SOX) deficiency is an inherited neurometabolic disorder biochemically characterized by tissue accumulation and high urinary excretion of sulfite and thiosulfate. Affected patients present severe neurological dysfunction accompanied by seizures, whose pathophysiology is poorly known. In the present study we evaluated the in vitro effects of sulfite and thiosulfate on important parameters of glutamatergic neurotransmission and redox homeostasis in rat cerebral cortex slices. We verified that sulfite, but not thiosulfate, significantly decreased glutamate uptake when cerebral cortex slices were exposed during 1h to these metabolites. We also observed that thiosulfate inhibited glutamine synthetase (GS) activity. A pronounced trend toward GS inhibition induced by sulfite was also found. Regarding redox homeostasis, sulfite, at the concentration of 10 muM, increased thiobarbituric acid-reactive substances and decreased glutathione concentrations after 1h of exposure. In contrast, thiosulfate did not alter these parameters. We also found that 500 muM sulfite increased sulfhydryl group content in rat cerebral cortex slices and increased GSH levels in a medium containing oxidized GSH (GSSG) and devoid of cortical slices, suggesting that sulfite reacts with disulfide bonds to generate sulfhydryl groups. Moreover, sulfite and thiosulfate did not alter the activities of glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST) and glucose-6-phosphate dehydrogenase (G6PDH) after 1h of incubation. However, sulfite inhibited the activities of GPx, GST and G6PDH when cortical slices were exposed for 3h to sulfite. We finally verified that sulfite did not induce cell death after 1h of incubation. Our data show that sulfite impairs glutamatergic neurotransmission and redox homeostasis in cerebral cortex. Therefore, it may be presumed that these pathomechanisms contribute, at least in part, to the seizures observed in patients affected by SOX deficiency. CI - Copyright (c) 2015 Elsevier Ltd. All rights reserved. FAU - Parmeggiani, Belisa AU - Parmeggiani B AD - Departamento de Bioquimica, Instituto de Ciencias Basicas da Saude, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 - Anexo - CEP, 90035-003 Porto Alegre, RS, Brazil. FAU - Moura, Alana Pimentel AU - Moura AP AD - Departamento de Bioquimica, Instituto de Ciencias Basicas da Saude, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 - Anexo - CEP, 90035-003 Porto Alegre, RS, Brazil. FAU - Grings, Mateus AU - Grings M AD - Departamento de Bioquimica, Instituto de Ciencias Basicas da Saude, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 - Anexo - CEP, 90035-003 Porto Alegre, RS, Brazil. FAU - Bumbel, Anna Paula AU - Bumbel AP AD - Departamento de Bioquimica, Instituto de Ciencias Basicas da Saude, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 - Anexo - CEP, 90035-003 Porto Alegre, RS, Brazil. FAU - de Moura Alvorcem, Leonardo AU - de Moura Alvorcem L AD - Departamento de Bioquimica, Instituto de Ciencias Basicas da Saude, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 - Anexo - CEP, 90035-003 Porto Alegre, RS, Brazil. FAU - Tauana Pletsch, Julia AU - Tauana Pletsch J AD - Departamento de Bioquimica, Instituto de Ciencias Basicas da Saude, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 - Anexo - CEP, 90035-003 Porto Alegre, RS, Brazil. FAU - Fernandes, Carolina Goncalves AU - Fernandes CG AD - Departamento de Bioquimica, Instituto de Ciencias Basicas da Saude, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 - Anexo - CEP, 90035-003 Porto Alegre, RS, Brazil. FAU - Wyse, Angela T S AU - Wyse AT AD - Departamento de Bioquimica, Instituto de Ciencias Basicas da Saude, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 - Anexo - CEP, 90035-003 Porto Alegre, RS, Brazil. FAU - Wajner, Moacir AU - Wajner M AD - Departamento de Bioquimica, Instituto de Ciencias Basicas da Saude, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 - Anexo - CEP, 90035-003 Porto Alegre, RS, Brazil; Servico de Genetica Medica, Hospital de Clinicas de Porto Alegre, Rua Ramiro Barcelos, 2350 - CEP, 90035-003 Porto Alegre, RS, Brazil. FAU - Leipnitz, Guilhian AU - Leipnitz G AD - Departamento de Bioquimica, Instituto de Ciencias Basicas da Saude, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 - Anexo - CEP, 90035-003 Porto Alegre, RS, Brazil. Electronic address: guilhian@ufrgs.br. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150313 PL - United States TA - Int J Dev Neurosci JT - International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience JID - 8401784 RN - 0 (Neurotransmitter Agents) RN - 0 (Sulfites) RN - 0 (Thiobarbituric Acid Reactive Substances) RN - 10028-17-8 (Tritium) RN - 3KX376GY7L (Glutamic Acid) RN - EC 1.1.1.27 (L-Lactate Dehydrogenase) RN - EC 1.1.1.49 (Glucosephosphate Dehydrogenase) RN - EC 1.11.1.9 (Glutathione Peroxidase) RN - EC 1.8.1.7 (Glutathione Reductase) RN - GAN16C9B8O (Glutathione) SB - IM MH - Animals MH - Cerebral Cortex/*drug effects MH - Dose-Response Relationship, Drug MH - Glucosephosphate Dehydrogenase/metabolism MH - Glutamic Acid/*metabolism MH - Glutathione/*metabolism MH - Glutathione Peroxidase/metabolism MH - Glutathione Reductase/metabolism MH - In Vitro Techniques MH - L-Lactate Dehydrogenase/metabolism MH - Neurotransmitter Agents/*metabolism MH - Oxidative Stress/drug effects MH - Protein Carbonylation/drug effects MH - Rats MH - Rats, Wistar MH - Sulfites/*pharmacology MH - Thiobarbituric Acid Reactive Substances/metabolism MH - Tritium/metabolism OTO - NOTNLM OT - Glutamatergic neurotransmission OT - Rat cerebral cortex OT - Redox homeostasis OT - Sulfite OT - Sulfite oxidase deficiency OT - Thiosulfate EDAT- 2015/03/18 06:00 MHDA- 2015/12/31 06:00 CRDT- 2015/03/18 06:00 PHST- 2015/01/14 00:00 [received] PHST- 2015/03/11 00:00 [revised] PHST- 2015/03/11 00:00 [accepted] PHST- 2015/03/18 06:00 [entrez] PHST- 2015/03/18 06:00 [pubmed] PHST- 2015/12/31 06:00 [medline] AID - S0736-5748(15)00033-7 [pii] AID - 10.1016/j.ijdevneu.2015.03.005 [doi] PST - ppublish SO - Int J Dev Neurosci. 2015 May;42:68-75. doi: 10.1016/j.ijdevneu.2015.03.005. Epub 2015 Mar 13.