Enhanced phosphatidylinositol 3-kinase (PI3K)/Akt signaling has pleiotropic targets in hippocampal neurons exposed to iron-induced oxidative stress

 

Autores
Uranga, Romina Maria; Katz, Sebastian; Salvador, Gabriela Alejandra
Tipo de recurso
artículo
Estado
Versión publicada
Año de publicación
2013
País
Argentina
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio
CONICET Digital (CONICET)
Descripción
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 on different molecular targets such as glycogen synthase kinase 3β (GSK3β) and Forkhead box-O (FoxO) transcription factors during mild oxidative stress triggered by iron overload. The exposure of mouse hippocampal neurons (HT22) to different concentrations of Fe 2+ (25-200 μM) for 24 h led us to define a mild oxidative injury status (50 μM Fe 2+ ) in which cell morphology showed changes typical of neuronal damage, with increased lipid peroxidation and cellular oxidant levels but no alteration of cellular viability. There was a simultaneous increase in both Akt and GSK3β phosphorylation. Levels of phospho-FoxO3a (inactive form) increased in the cytosolic fraction of cells treated with iron in a PI3K-dependent manner. Moreover, PI3K and Akt translocated to the nucleus in response to oxidative stress. Iron-overloaded cells harboring a constitutively active form of Akt showed decreased oxidants levels. Indeed, glutathione (GSH) synthesis under oxidative stress conditions was regulated by activated Akt. Our results show that activation of the PI3K/Akt pathway during iron-induced neurotoxicity regulates multiple targets such as GSK3β, FoxO transcriptional activity and glutathione metabolism thus modulating neuronal response to oxidative stress.
Idioma
inglés
OAI Identifier
oai:ri.conicet.gov.ar:11336/4534
Enlace del recurso
http://hdl.handle.net/11336/4534
Nivel de acceso
Acceso abierto
Materia
NEURODEGENERATION
OXIDATIVE STRESS
PI3K
FOXO
Bioquímica y Biología Molecular
Ciencias Biológicas
CIENCIAS NATURALES Y EXACTAS