The effect of DNA methylation inhibitors on 1-methyl-4-phenylpyridinium iodide (MPP +) induced neurotoxicity in cultured neuronal cells model

Author(s)

Rebeca Araujo Cantelmo

• Document type: Master's Dissertation
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC)
• Defense date: 2017-10-09

Examining board members

Sâmia Regiane Lourenço Joca; Lusania Maria Greggi Antunes; Cláudio da Cunha; Marcela Bermudez Echeverry

• Advisor: Sâmia Regiane Lourenço Joca; Antonio Cardozo dos Santos

Abstract

Parkinson\'s disease is the second most common neurodegenerative disease nowadays. About 10% of the disease cases are related to genetic factors and the other 90% are due to environmental and epigenetic factors. Evidence indicates changes in DNA methylation in genes related to the development of Parkinson\'s disease. However, the effect of DNA methylation inhibitors on MPP+-induced neurotoxicity, a drug that mimics neurodegenerative processes associated with Parkinson\'s in vitro, is not known. The aim of this study was to evaluate the effect of DNA methylation inhibitors (RG108, N-phthalyl-L-tryptophan and 5azadC, 5-aza-2?-deoxycytidine) and of the universal donor of methyl group (SAM, S-adenosyl methionine) on: 1. MPP+ -induced neurotoxicity in culture of immortalized cells (PC12), by analysis of cell viability in the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium) test; 2. neuritogenesis, in the presence and absence of MPP +. Results indicated that: 1. treatment with DNMTi or SAM induced effects per se on cell viability only at higher concentrations and after prolonged periods of incubation (24h); 2. DNMTi (DNA methyltransferase inhibitors) and SAM increased cell differentiation and neuritogenesis per se, especially when incubated for 30 minutes, as well as they potentiated NGF-induced neurogenesis; 3. the drugs attenuated MPP+-induced effects on neuritogenesis. Altogether, these data suggests short treatment with both DNMTi and SAM do not cause cellular cytotoxicity (cell death), but are able to increase neuritogenesis (cell differentiation) and protect against MPP+-induced neurotoxicity in differentiated cells. (AU)

• FAPESP's process: 15/05530-3 - The effect of DNA methylation inhibitors on 1-methyl-4-phenylpyridinium iodide (MPP +) induced neurotoxicity in cultured neuronal cells model.
• Grantee: Rebeca Araujo Cantelmo
• Support Opportunities: Scholarships in Brazil - Master