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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Yshii, Lidia M. [1] ; Denadai-Souza, Alexandre [2] ; Vasconcelos, Andrea R. [1] ; Avellar, Maria Christina W. [2] ; Scavone, Cristoforo [1]
Total Authors: 5
Affiliation:
[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
Total Affiliations: 2
Document type: Journal article
Source: JOURNAL OF NEUROINFLAMMATION; v. 12, OCT 26 2015.
Web of Science Citations: 5
Abstract

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)

FAPESP's process: 11/10303-5 - TRAF6 and alfa-synuclein interaction and the subsequent modulation of signaling pathways
Grantee:Lidia Mitiko Yshii
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 11/12255-8 - Influence of TLR4 receptors in behavioral and neurochemical alterations caused by intermittent fasting in C3H/HeJ mice
Grantee:Andrea Rodrigues Vasconcelos
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 09/12375-3 - Role of the protein SPAG11 in the modulation of experimental arthritis
Grantee:Alexandre Denadai Souza
Support Opportunities: Scholarships in Brazil - Post-Doctoral