Open AccessInsulin‐activated Akt rescues Aβ oxidative stress‐induced cell death by orchestrating molecular trafficking
Author(s) -
Picone Pasquale,
Giacomazza Daniela,
Vetri Valeria,
Carrotta Rita,
Militello Valeria,
Biagio Pier L. San,
Di Carlo Marta
Publication year - 2011
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/j.1474-9726.2011.00724.x
Subject(s) - protein kinase b , microbiology and biotechnology , biology , mitochondrial permeability transition pore , oxidative stress , mitochondrion , phosphorylation , insulin receptor , programmed cell death , insulin , apoptosis , proto oncogene proteins c akt , signal transduction , reactive oxygen species , biochemistry , endocrinology , insulin resistance
Summary Increasing evidence indicates that Alzheimer’s disease, one of the most diffused aging pathologies, and diabetes may be related. Here, we demonstrate that insulin signalling protects LAN5 cells by amyloid‐β42 (Aβ)‐induced toxicity. Aβ affects both activation of insulin receptors and the levels of phospho‐Akt, a critical signalling molecule in this pathway. In contrast, oxidative stress induced by Aβ can be antagonized by active Akt that, in turn, inhibits Foxo3a, a pro‐apoptotic transcription factor activated by reactive oxygen species generation. Insulin cascade protects against mitochondrial damage caused by Aβ treatment, restoring the mitochondrial membrane potential. Moreover, we show that the recovery of the organelle integrity recruits active Akt translocation to the mitochondrion. Here, it plays a role both by maintaining unimpaired the permeability transition pore through increase in HK‐II levels and by blocking apoptosis through phosphorylation of Bad, coming from cytoplasm after Aβ stimulus. Together, these results indicate that the Akt survival signal antagonizes the Aβ cell death process by balancing the presence and modifications of common molecules in specific cellular environments.