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 viability per 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 differentiation per 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).
Assuntos
1-Metil-4-fenilpiridínio/toxicidade , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurotoxinas/toxicidade , S-Adenosilmetionina/toxicidade , 1-Metil-4-fenilpiridínio/administração & dosagem , Animais , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Neurônios Dopaminérgicos/patologia , Relação Dose-Resposta a Droga , Neurotoxinas/administração & dosagem , Células PC12 , Ratos , S-Adenosilmetionina/administração & dosagemRESUMO
Being an elite athlete is an extremely coveted position, which can lead an individual to use doping. As knowledge is extended, doping techniques have become increasingly sophisticated, and the newest method of doping is gene doping. This article aims to present an updated bibliographic survey that addresses gene doping between 1983 and 2018. Anti-doping agencies have not yet approved any detection technique for this type of doping. The possibility of eradicating such doping is almost zero mainly because gene therapy advances rapidly. In this scenario, the future of gene doping must be discussed and decided before irreversible limits are exceeded.
