Protein aggregation containing beta-amyloid, alpha-synuclein and hyperphosphorylated tau in cultured cells of hippocampus, substantia nigra and locus coeruleus after rotenone exposure

Autor(es)

Chaves, Rodrigo S. ^[1] ; Melo, Thaiany Q. ^[1] ; Martins, Stephanie A. ^[1] ; Ferrari, Merari F. R. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med, Dept Neurol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BMC NEUROSCIENCE; v. 11, NOV 10 2010.
• Citações Web of Science: 23

Resumo

Background: Protein aggregates containing alpha-synuclein, beta-amyloid and hyperphosphorylated tau are commonly found during neurodegenerative processes which is often accompanied by the impairment of mitochondrial complex I respiratory chain and dysfunction of cellular systems of protein degradation. In view of this, we aimed to develop an in vitro model to study protein aggregation associated to neurodegenerative diseases using cultured cells from hippocampus, locus coeruleus and substantia nigra of newborn Lewis rats exposed to 0.5, 1, 10 and 25 nM of rotenone, which is an agricultural pesticide, for 48 hours. Results: We demonstrated that the proportion of cells in culture is approximately the same as found in the brain nuclei they were extracted from. Rotenone at 0.5 nM was able to induce alpha-synuclein and beta amyloid aggregation, as well as increased hyperphosphorylation of tau, although high concentrations of this pesticide (over 1 nM) lead cells to death before protein aggregation. We also demonstrated that the 14kDa isoform of alpha-synuclein is not present in newborn Lewis rats. Conclusion: Rotenone exposure may lead to constitutive protein aggregation in vitro, which may be of relevance to study the mechanisms involved in idiopathic neurodegeneration. (AU)

• Processo FAPESP: 08/04480-9 - Análise do tráfego intracelular de mitocôndrias antes da formação de agregados protéicos em neurodegeneração
• Beneficiário: Merari de Fátima Ramires Ferrari
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 09/00010-0 - Análise do RNAm de proteínas do transporte retrógrado e ancoragem de mitocôndrias antes da formação de agregados protéicos envolvidos em neurodegeneração
• Beneficiário: Stephanie Alves Martins
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 08/04655-3 - Estudo do transporte retrógrado e ancoramento de mitocôndrias em cultura de células do hipocampo, substância negra e locus coeruleus antes da formação de agregados protéicos envolvidos em neurodegeneração
• Beneficiário: Rodrigo dos Santos Chaves
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 09/02345-0 - Estudo da expressão de proteínas relacionadas ao transporte anterógrado de mitocôndrias anterior à formação de agregados protéicos envolvidos em neurodegeneração
• Beneficiário: Thaiany Quevedo Melo
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica