title: Reactive Oxygen Species Evoked by Potassium Deprivation and Staurosporine Inactivate Akt and Induce the Expression of TXNIP in Cerebellar Granule Neurons.
abstract: The reactive oxygen species (ROS) play a critical role in neuronal apoptosis; however, the mechanisms are not well understood. It has been shown that thioredoxin-interacting protein (TXNIP) overexpression renders cells more susceptible to oxidative stress and promotes apoptosis and that the activation of PI3K/Akt pathway leads to a downregulation of TXNIP. Here, we evaluated the role of ROS in the regulation of Akt activity and the subsequent regulation of the TXNIP expression in a model of apoptotic death of cerebellar granule neurons (CGN). We observed that two apoptotic conditions that generate ROS at short times led to an increase in the expression of TXNIP in a time-dependent manner; antioxidants significantly reduced this expression. Also, H2O2caused an increase in TXNIP expression. Moreover, apoptotic conditions induced inactivation of Akt in a time-dependent manner similar to TXNIP expression and H2O2treatment led to Akt inactivation. Besides, the pharmacological inhibition of Akt increases TXNIP expression and induces CGN cell death. Together, these results suggest that ROS promote neuronal apoptosis through the Akt-TXNIP signaling pathway, supporting the idea that the PI3K/Akt pathway regulates the TXNIP expression. This study highlights the potential importance of this mechanism in neuronal death.
authors.affiliation: División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad de México, Mexico.
authors.forename: Marco Antonio
authors.identifier: 0000-0002-8415-0799
authors.initials: MA
authors.lastname: Zaragoza-Campillo
authors.affiliation: División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad de México, Mexico.
authors.forename: Julio
authors.identifier: 0000-0003-4880-8597
authors.initials: J
authors.lastname: Morán
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D003470:Culture Media / Q000737:chemistry; D015870:Gene Expression / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000633:toxicity; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology*
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D003470:Culture Media; D017382:Reactive Oxygen Species; C493796:TXNIP protein, rat; D006861:Hydrogen Peroxide; D051057:Proto-Oncogene Proteins c-akt; D019311:Staurosporine; D011188:Potassium