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

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).