MPP+-induced cytotoxicity in neuroblastoma cells: Antagonism and reversal by guanosine

摘要: Guanosine exerts neuroprotective effects in the central nervous system. Apoptosis, a morphological form of programmed cell death, is implicated pathophysiology Parkinson’s disease (PD). MPP+, dopaminergic neurotoxin, produces vivo and vitro cellular changes characteristic PD, such as cytotoxicity, resulting apoptosis. Undifferentiated human SH-SY5Y neuroblastoma cells had been used an model disease. We investigated if extracellular guanosine affected MPP+-induced cytotoxicity examined molecular mechanisms mediating its effects. Exposure to MPP+ (10 μM–5 mM for 24–72 h) induced DNA fragmentation time-dependent manner (p < 0.05). Administration (100 μM) before, concomitantly with or, importantly, after addition abolished fragmentation. Addition (500 μM) increased caspase-3 activity over 72 h (p < 0.05), this was by pre- or co-treatment guanosine. pertussis toxin prior eliminated anti-apoptotic effect guanosine, indicating that dependent on Gi protein-coupled receptor, most likely putative receptor. The protection also selective inhibitor enzyme PI-3-K/Akt/PKB (LY294002), confirming pathway plays decisive role Neither nor any significant α-synuclein expression. Thus, antagonizes reverses via activation survival pathway, PI-3-K/Akt/PKB. Our results suggest may be effective pharmacological intervention PD.