INVESTIGADORES
URANGA Romina Maria
congresos y reuniones científicas
Título:
Protective role of PI3K/Akt pathway during iron-induced oxidative stress in hippocampal neurons
Autor/es:
URANGA, ROMINA MARÍA; SÁNCHEZ CAMPOS, SOFÍA; SALVADOR, GABRIELA ALEJANDRA
Reunión:
Congreso; VIII International Congress of the Society for Free Radical Biology and Medicine; 2013
Resumen:
The phosphatidylinositol 3-kinase (PI3K)/Akt pathway is a key component
in synaptic plasticity and neuronal survival. The aim of this work was to
investigate the participation of the PI3K/Akt pathway and its outcome during
mild oxidative stress triggered by iron overload in hippocampal neurons (HT22).
The exposure of HT22
cells to different concentrations of Fe2+ (25-200 microM) for 24 h led us to define a mild
oxidative injury status (50 microM Fe2+) in which cell lipid peroxidation
and cellular oxidant levels increased with no alteration of cellular
viability. The presence of iron caused an increase in the phosphorylation
levels of Akt. The inhibition of PI3K/Akt pathway (LY294002/Akt inh IV) led to increased levels of
oxidative stress, which were prevented in the presence of a constitutively active
form of Akt. SOD1 and SOD2 expression strongly decreased during iron-induced
oxidative stress in a PI3K-dependent manner. In the presence of iron, glutathione (GSH) levels did not show significant changes, however gamma-glutamylcysteine synthetase catalytic subunit (gamma-GCSc) levels increased. This
rise in gamma-GCSc was abolished by
LY294002. Results show that PI3K/Akt pathway plays a key role in neuronal
survival by protecting cells from ROS generation through GSH metabolism
regulation.