FOXO transcription factors in antioxidant defense

Abstract

Forkhead box, class O (FOXO) family proteins are widely expressed and highly conserved transcriptional regulators that modulate cellular fuel metabolism, stress resistance and cell death. FOXO target genes include genes encoding antioxidant proteins, thus likely contributing to the key role FOXOs play in the cellular response to oxidative stress and supporting the cellular strategies of antioxidant defense, that is, prevention (of the formation of reactive oxygen species), interception (of reactive species prior to their reaction with cellular components), repair (of damaged biomolecules), and adaptation (i.e., the stimulation of signaling pathways allowing for the expression of protective proteins). FOXOs themselves are regulated by redox processes at several levels, including expression of FOXO genes and enzymatic as well as nonenzymatic posttranslational modifications of FOXO proteins. The latter include modifications of FOXO cysteine residues. Here, an overview is provided on (i) the contribution of FOXO target genes to cellular antioxidative strategies, and (ii) on the impact of thiol homeostasis and thiol modification on FOXO activity.

Chromosome-level genome of black cutworm provides novel insights into polyphagy and seasonal migration in insects

“…S6A). Among the genes for signal transduction pathway, the FoxO family of transcription factors, which regulate the expression of genes in many important physiological events including cell cycle (CC), oxidative stress resistance/DNA repair (OR), immune-regulation (IR), and apoptosis (AP) [ 19 ], was chosen for a more detailed analysis of gene expansion (Additional file 2 : Fig. S6B).…”

Heterozygous Loss of KRIT1 in Mice Affects Metabolic Functions of the Liver, Promoting Hepatic Oxidative and Glycative Stress

“…On the other hand, our previous studies in cellular models demonstrated that KRIT1 influenced, directly and dose-dependently, the expression levels of FoxO1, as well as demonstrating that this relationship was strictly correlated with the maintenance of intracellular ROS homeostasis [ 15 ]. Accordingly, FoxO1 is known to be a master transcriptional regulator of cellular responses to ROS and oxidative stress through the induction of genes encoding antioxidant enzymes, including SOD2 and catalase [ 15 , 40 ]. Interestingly, besides its role in antioxidant responses and oxidative stress resistance, it has been established that the FoxO1 transcription factor also plays a key role in insulin signaling and hepatic glucose metabolism [ 34 , 41 , 42 ], suggesting the possible implication of KRIT1 in critical FoxO1-dependent metabolic pathways in the liver.…”

“…Alterations in hepatic glucose metabolism and mitochondrial oxidative phosphorylation are tightly interconnected with changes in redox homeostasis and signaling, and may result in decreased hepatic antioxidant defenses and increased oxidative stress [ 68 , 69 ]. Indeed, whereas the rates of aerobic metabolism and ROS production are positively correlated, the intimate liaison between redox and metabolic pathways is highlighted by their sharing of master regulators, including FoxO1 [ 33 , 40 ]. Therefore, we addressed whether the observed alterations in hepatic glucose metabolism caused by heterozygous loss of KRIT1 in mice were associated with changes in major determinants of hepatic antioxidant defenses, including Nrf2, the master regulator of the antioxidant transcriptional response [ 70 ], and glutathione (GSH), the predominant antioxidant molecule and main regulator of cellular redox status in the liver [ 71 ].…”

Chili-supplemented food decreases glutathione-S-transferase activity in Drosophila melanogaster females without a change in other parameters of antioxidant system

“…The extension of lifespan in fruit fly cohorts by regular consumption of chili-supplemented food can be conferred by the activation of well-known pro-survival pathways. In particular, a number of plant preparations activate the transcription factor FOXO (forkhead box O), increasing the expression of proteins that are necessary to overcome stress conditions [ 1 , 21 ]. Lifespan extension is also achieved by the inhibition of mTOR (mechanistic target of rapamycin) kinase, that activates autophagy [ 22 ].…”

“…The appearance of the effect only in males may imply that the signaling pathway plays an important role for this gender. Genes that encode antioxidant enzymes, including SOD, are targets for the transcription factors FOXO and Nrf2 in mammals [ 21 , 28 , 29 ]. However, much less is known about regulation of antioxidant enzyme expression in fruit flies.…”