@article{2980551,
    title = "Enhanced Ca2+ Entry Sustains the Activation of Akt in Glucose Deprived SH-SY5Y Cells",
    author = "Kourti, M. and Liaropoulou, D. and Paschou, M. and Giagklisi, I. and Paschalidi, M. and Petani, E. and Papazafiri, P.",
    journal = "International Journal of Molecular Sciences",
    year = "2022",
    volume = "23",
    number = "3",
    publisher = "MDPI",
    issn = "1422-0067",
    doi = "10.3390/ijms23031386",
    abstract = "The two crucial cellular insults that take place during cerebral ischemia are the loss of oxygen and loss of glucose, which can both activate a cascade of events leading to neuronal death. In addition, the toxic overactivation of neuronal excitatory receptors, leading to Ca2+ overload, may contribute to ischemic neuronal injury. Brain ischemia can be simulated in vitro by oxygen/glucose deprivation, which can be reversible by the re-establishment of physiological conditions. Accordingly, we examined the effects of glucose deprivation on the PI3K/Akt survival signaling pathway and its crosstalk with HIF-1α and Ca2+ homeostasis in SH-SY5Y human neuroblastoma cells. It was found that glucose withdrawal decreased HIF-1α protein levels even in the presence of the ischemiamimicking CoCl2. On the contrary, and despite neuronal death, we identified a strong activation of the master pro-survival kinase Akt, a finding that was also confirmed by the increased phosphorylation of GSK3, a direct target of p-Akt. Remarkably, the elevated Ca2+ influx recorded was found to promptly trigger the activation of Akt, while a re-addition of glucose resulted in rapid restoration of both Ca2+ entry and p-Akt levels, highlighting the plasticity of neurons to respond to ischemic challenges and the important role of glucose homeostasis for multiple neurological disorders. © 2022 by the authors. Licensee MDPI, Basel, Switzerland."
}