| Popis: |
Copper, a transition metal with essential biological functions, exerts neurotoxic effects when present in excess. The aim of the present study was to explore the effects of quercetin, a plant-derived flavonoid and one of the most potent scavengers of reactive oxygen species (ROS), on the survival of differentiated P19 neurons exposed to high concentrations of copper ions. The obtained results indicate that effects of quercetin were determined by the severity of toxic insult. In moderately injured neurons exposed to 0.5 mM CuSO4 for 24 hours, 150 μM quercetin increased viability of P19 neurons by preventing ROS production, caspase-3/7 activity and chromatin condensation. Neuroprotective effect of quercetin on the survival of P19 neurons was prevented in the presence of wortmannin, an inhibitor of the PI3K/Akt signalling pathway. Treatment with 1 mM CuSO4 induced severe decrease in neuronal survival, due to very pronounced ROS accumulation, caspase-3/7 activation, and changed expression of genes involved in intracellular signalling and induction of apoptosis (p53, c-fos, Bcl-2 and Bax). In these conditions presence of 150 μM quercetin failed to affect neuronal survival, while 30 μM quercetin demonstrated strong pro-oxidative action and further exacerbated cytotoxic effects of copper, as evidenced by additional decrease in neuronal viability and very pronounced increase in ROS formation. The obtained results indicate the dual nature of quercetin action in copper-driven neurodegeneration. Both findings should be considered in the future development of novel antioxidative therapeutic strategies based on polyphenolic structures. |
