Role of FOXO3a Transcription Factor in the Regulation of Liver Oxidative Injury

Abstract

Oxidative stress has been identified as a key mechanism in liver damage caused by various chemicals. The transcription factor FOXO3a has emerged as a critical regulator of redox imbalance. Multiple post-translational changes and epigenetic processes closely regulate the activity of FOXO3a, resulting in synergistic or competing impacts on its subcellular localization, stability, protein–protein interactions, DNA binding affinity, and transcriptional programs. Depending on the chemical nature and subcellular context, the oxidative-stress-mediated activation of FOXO3a can induce multiple transcriptional programs that play crucial roles in oxidative injury to the liver by chemicals. Here, we mainly review the role of FOXO3a in coordinating programs of genes that are essential for cellular homeostasis, with an emphasis on exploring the regulatory mechanisms and potential application of FOXO3a as a therapeutic target to prevent and treat liver oxidative injury.

Identification of putative promoter elements for epsilon glutathione s-transferases genes associated with resistance to DDT in the malaria vector mosquito anopheles arabiensis

“…The DNA sequences designated as environmental response element are speculated to be involved in the induction of gene expression in response to hormonal signals or environmental stimuli [ 23 , 33 ]. Several transcription factors responsive to oxidative stress, including Forkhead transcription factor Fox L1 [ 34 ] and NF – kb (36) and AhR [ 35 ] were identified in the GSTe1 and GSTe2 promoters in both the resistant and susceptible strains of An. arabiensis .…”

Exposure to the pesticide tefluthrin causes developmental neurotoxicity in zebrafish

“…These factors play a role in liver function and disease (66). Furthermore, FOXO(s) play a critical role in protecting the liver against the development of NAFLD (67) and liver oxidative injury (68). In conclusion, the data indicates that tefluthrin exposure results in liver toxicity resulting in a transcriptomic response to mitigate the toxicity induced.…”

TMF suppresses chondrocyte hypertrophy in osteoarthritic cartilage by mediating the FOXO3a/BMPER pathway

“…There are four elements in the FOXO sub-family: Namely, FOXO1, FOXO3a, FOXO4 and FOXO6. FOXO3a activity is regulated by post-translational modifications, such as acetylation, phosphorylation and ubiquitination (20). The results of a previous study revealed that histone deacetylases, such as Sirt1 and Sirt3, deacetylate FOXO3a and mediate its transcriptional activity (21).…”