Dual effects of S-adenosyl-methyonine on PC12 cells exposed to the dopaminergic neurotoxin MPP+

Autor(es)

Cantelmo, Rebeca Araujo ^[1] ; dos Santos, Neife Aparecida G. ^[2] ; dos Santos, Antonio Cardozo ^[2] ; Joca, Samia Regiane Lourenco ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto FCFRP, Dept Biomol Sci, Ave Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto FCFRP, Dept Clin Toxicol & Bromatol Anal, Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Pharmacy and Pharmacology; v. 72, n. 10 JUN 2020.
• Citações Web of Science: 0

Resumo

Objectives To investigate S-adenosyl-methyonine (SAM) effects on PC12 cells viability and neuritogenesis treated with MPP+ (1-methyl-4-phenylpyridinium). Methods PC12 cell viability test (MTT assay) in DMEM medium with SAM and/or MPP+; PC12 cell neuritogenesis test in F-12K medium with nerve growth factor (NGF); DNMT activity in PC12 cells (DNMT Activity Assay Kit) with SAM and/or MPP+. Key findings (1) MPP+ decreased cell viability; (2) SAM did not affect cell viabilityper se, but it increased MPP+ neurotoxicity when co-incubated with the neurotoxin, an effect abolished by DNA methyltransferases (DNMT) inhibitors; (3) pretreatment with SAM for 30 min or 24 h before MPP+ addition had no effect on cell viability. Neuritogenesis: Treatment with SAM for 30 min or 24 h (1) increased cell differentiationper se, (2) increased NGF differentiating effects (additive effect) and (3) blocked the neuritogenesis impairment induced by MPP+. SAM with MPP+ increased the DNMT activity, whereas SAM alone or MPP+ alone did not. Conclusions (1) SAM might induce neurotoxic or neuroprotective effects on PC12 cells, depending on the exposure conditions; (2) DNMT inhibitors might attenuate the MPP+ exacerbation toxicity induced by SAM; (3) DNA methylation might be involved in the observed effects of SAM (needs further investigation). (AU)

• Processo FAPESP: 15/05530-3 - Efeito de inibidores da metilação de DNA sobre a neurotoxicidade induzida por Iodeto de 1-metil-4-fenilpiridínio (MPP+) em modelo de células neuroniais
• Beneficiário: Rebeca Araujo Cantelmo
• Modalidade de apoio: Bolsas no Brasil - Mestrado