Induction of foxo3a protects turtle neurons against oxidative stress

• Published in: Comparative biochemistry and physiology. Part A, Molecular & integrative physiology Vol. 243; p. 110671
• Main Authors: Reiterer, Melissa, Milton, Sarah L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2020
• Subjects: Animals; Catechin - analogs & derivatives; Catechin - pharmacology; Epigallochatechin-3-gallate; Forkhead Box Protein O3 - genetics; Forkhead Box Protein O3 - metabolism; Hypoxia - physiopathology; Neurons - drug effects; Neurons - metabolism; Neurons - pathology; Neuroprotective Agents - pharmacology; Oxidative Stress; Oxygen - metabolism; Reactive oxygen species; Reoxygenation; Trachemys scripta; Turtles - metabolism; Trachemys scripta; Epigallochatechin-3-gallate; Reactive oxygen species; Reoxygenation
• ISSN: 1095-6433; 1531-4332
• DOI: 10.1016/j.cbpa.2020.110671

The detrimental effects of oxidative stress caused by the accumulation of Reactive Oxygen Species (ROS) factor into aging, senescence and several neurodegenerative diseases. Mammalian models are extremely susceptible to the stresses that follow the restoration of oxygen after anoxia; however some organisms including the freshwater turtle Trachemys scripta can withstand extended anoxia and reoxygenation without apparent pathology. The ability of the turtle to withstand these conditions is thought to be linked to the upregulation of protective mechanisms such as heat shock proteins (HSP) as well as the suppression of ROS formation and the upregulation of antioxidant defenses. One such antioxidant mechanism is the transcription factor Forkhead box O3a (FOXO3a), that has been shown to be activated in several animal models during oxidative stress. In this study, we utilized both the transfection of a plasmid carrying foxo3a and the pharmacological manipulation of foxo3a using the green tea extract Epigallocatechin-3-gallate (EGCG) to investigate the protective role of FOXO3a in the turtle brain. Our studies found that transcript levels of foxo3a were upregulated significantly during reoxygenation with greater increases during chemical oxidative stress. Induction of foxo3a by direct transfection significantly decreased cell death during chemical oxidative stress. Cells treated with EGCG also showed increased foxo3a expression and decreased cell death in the presence of H2O2. These results agree with results seen in other animal models and suggest that EGCG (through the upregulation of foxo3a) may be a therapeutic target against oxidative stress damage that warrants further investigation. [Display omitted] •Trachemys scripta neurons are highly resistant to anoxia and reoxygenation•foxo3a induction in turtle neuronal cultures decreases cell death during oxidative stress•EGCG treatment activates foxo3a expression during oxidative stress•EGCG decreases cell death during oxidative stress possibly through foxo3a activation