Suppression of MAPK attenuates neuronal cell death induced by activated glia-conditioned medium in alpha-synuclein overexpressing SH-SY5Y cells

Autor(es)

Yshii, Lidia M. ^[1] ; Denadai-Souza, Alexandre ^[2] ; Vasconcelos, Andrea R. ^[1] ; Avellar, Maria Christina W. ^[2] ; Scavone, Cristoforo ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci ICB 1, Mol Neuropharmacol Lab, Dept Pharmacol, BR-05508900 Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Sect Expt Endocrinol, Dept Pharmacol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF NEUROINFLAMMATION; v. 12, OCT 26 2015.
• Citações Web of Science: 5

Resumo

Background: Parkinson's disease (PD) is a neurodegenerative disease with characteristics and symptoms that are well defined. Nevertheless, its aetiology remains unknown. PD is characterized by the presence of Lewy bodies inside neurons. alpha-Synuclein (alpha-syn) is a soluble protein present in the pre-synaptic terminal of neurons. Evidence suggests that alpha-syn has a fundamental role in PD pathogenesis, given that it is an important component of Lewy bodies localized in the dopaminergic neurons of PD patients. Methods: In the present study, we investigated the influence of wild type (WT) and A30P alpha-syn overexpression on neuroblastoma SH-SY5Y toxicity induced by the conditioned medium (CM) from primary cultures of glia challenged with lipopolysaccharide (LPS) from Escherichia coli. Results: We observed that SH-SY5Y cells transduced with alpha-syn (WT or A30P) and treated with CM from LPS-activated glia cells show evidence of cell death, which is not reverted by NF-kappa B inhibition by sodium salicylate or by blockage of P50 (NF-kappa B subunit). Furthermore, the expression of A30P alpha-syn in neuroblastoma SH-SY5Y decreases the cell death triggered by the CM of activated glia versus WT alpha-syn or control group. This effect of A30P alpha-syn may be due to the low MAPK42/44 phosphorylation. This finding is substantiated by MEK1 inhibition by PD98059, decreasing LDH release by CM in SH-SY5Y cells. Conclusion: Our results suggest that SH-SY5Y cells transduced with alpha-syn (WT or A30P) and treated with CM from LPS-activated glia cells show cell death, which is not reverted by NF-kappa B blockage. Additionally, the expression of A30P alpha-syn on neuroblastoma SH-SY5Y leads to decreased cell death triggered by the CM of activated glia, when compared to WT alpha-syn or control group. The mechanism underlying this process remains to be completely elucidated, but the present data suggest that MAPK42/44 phosphorylation plays an important role in this process. (AU)

• Processo FAPESP: 12/50165-3 - Investigação do papel de TRAF6 na interação com alfa-sinucleína e na consequente modulação em vias de sinalização
• Beneficiário: Cristoforo Scavone
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 09/12375-3 - Papel da proteína SPAG11 na modulação da artrite experimental
• Beneficiário: Alexandre Denadai Souza
• Linha de fomento: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 11/12255-8 - Influência do receptor TLR4 nos efeitos comportamentais e bioquímicos induzidos pela dieta intermitente em camundongos C3H/HeJ
• Beneficiário: Andrea Rodrigues Vasconcelos
• Linha de fomento: Bolsas no Brasil - Doutorado
• Processo FAPESP: 11/10303-5 - Investigação do papel de TRAF6 na interação com alfa-sinucleína e na consequente modulação em vias de sinalização
• Beneficiário: Lidia Mitiko Yshii
• Linha de fomento: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 09/53527-0 - Alterações induzidas pelo meio condicionado proveniente da cultura primária de glia ativada pelo LPS na sinalização do NF-kB em células SH-SY5Y transduzidas com alfa-sinucleína
• Beneficiário: Cristoforo Scavone
• Linha de fomento: Auxílio à Pesquisa - Regular