FOXO transcription factors: key regulators of cell fate

2006 ◽  
Vol 34 (5) ◽  
pp. 722-726 ◽  
Author(s):  
E.W.-F. Lam ◽  
R.E. Francis ◽  
M. Petkovic
Keyword(s):  
Oxidative Stress ◽  
Drug Resistance ◽  
Transcription Factors ◽  
Cell Fate ◽  
Environmental Cues ◽  
Cellular Functions ◽  
Forkhead Box ◽  
Foxo Transcription Factors ◽  
Stress Damage

FOXO (forkhead box O) transcription factors are crucial regulators of cell fate. This function of FOXO proteins relies on their ability to control diverse and at times, opposing cellular functions, such as proliferation, differentiation, DNA repair, defence against oxidative stress damage and apoptosis, in response to hormones, growth factors and other environmental cues. This review discusses our current understanding of the regulation and role of FOXO transcription factors in determining cell fate and highlights their relevance to tumorigenesis and drug resistance.

FoxO transcription factors in oxidative stress response and ageing – a new fork on the way to longevity?

2008 ◽  
Vol 389 (3) ◽  
pp. 279-283 ◽  
Author(s):  
Daniel G. Sedding
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Cellular Functions ◽  
Post Translational Modifications ◽  
Cellular Effects ◽  
Forkhead Box ◽  
Foxo Transcription Factors

Abstract Forkhead box O (FoxO) transcription factors are important downstream targets of the PI3K/Akt signaling pathway and crucial regulators of cell fate. This function of FoxOs relies on their ability to control diverse cellular functions, including proliferation, differentiation, apoptosis, DNA repair, defense against oxidative stress and ageing. FoxOs are regulated by a variety of different growth factors and hormones, and their activity is tightly controlled by post-translational modifications, including phosphorylation, acetylation, ubiquitination and interaction with different proteins and transcription factors. This brief review focuses on the molecular mechanisms, cellular effects and resulting organismal phenotypes generated by differentially regulated FoxO proteins and discusses our current understanding of the role of FoxOs in disease and ageing processes.

scholarly journals Role of Forkhead Box O Transcription Factors in Oxidative Stress-Induced Chondrocyte Dysfunction: Possible Therapeutic Target for Osteoarthritis?

2018 ◽  
Vol 19 (12) ◽  
pp. 3794 ◽  
Author(s):  
Rikang Wang ◽  
Gang Chen ◽  
Shuai Zhang ◽  
Rahul Previn ◽  
Di Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Molecular Targets ◽  
Protective Role ◽  
Matrix Synthesis ◽  
Forkhead Box ◽  
Foxo Transcription Factors ◽  
And Oxidative Stress ◽  
Made In

Chondrocyte dysfunction occurs during the development of osteoarthritis (OA), typically resulting from a deleterious increase in oxidative stress. Accordingly, strategies for arresting oxidative stress-induced chondrocyte dysfunction may lead to new potential therapeutic targets for OA treatment. Forkhead box O (FoxO) transcription factors have recently been shown to play a protective role in chondrocyte dysfunction through the regulation of inflammation, autophagy, aging, and oxidative stress. They also regulate growth, maturation, and matrix synthesis in chondrocytes. In this review, we discuss the recent progress made in the field of oxidative stress-induced chondrocyte dysfunction. We also discuss the protective role of FoxO transcription factors as potential molecular targets for the treatment of OA. Understanding the function of FoxO transcription factors in the OA pathology may provide new insights that will facilitate the development of next-generation therapies to prevent OA development and to slow OA progression.

scholarly journals FOXO Transcriptional Factors and Long-Term Living

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Ghulam Murtaza ◽  
Abida Kalsoom Khan ◽  
Rehana Rashid ◽  
Saiqa Muneer ◽  
Syed Muhammad Farid Hasan ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Healthy Aging ◽  
Growth Stress ◽  
Human Longevity ◽  
Growth Factor Signaling ◽  
Forkhead Box ◽  
Foxo Transcription Factors ◽  
Genetic And Environmental Factors

Several pathologies such as neurodegeneration and cancer are associated with aging, which is affected by many genetic and environmental factors. Healthy aging conceives human longevity, possibly due to carrying the defensive genes. For instance, FOXO (forkhead box O) genes determine human longevity. FOXO transcription factors are involved in the regulation of longevity phenomenon via insulin and insulin-like growth factor signaling. Only one FOXO gene (FOXO DAF-16) exists in invertebrates, while four FOXO genes, that is, FOXO1, FOXO3, FOXO4, and FOXO6 are found in mammals. These four transcription factors are involved in the multiple cellular pathways, which regulate growth, stress resistance, metabolism, cellular differentiation, and apoptosis in mammals. However, the accurate mode of longevity by FOXO factors is unclear until now. This article describes briefly the existing knowledge that is related to the role of FOXO factors in human longevity.

scholarly journals Role of Forkhead Transcription Factors in Diabetes-Induced Oxidative Stress

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Bhaskar Ponugoti ◽  
Guangyu Dong ◽  
Dana T. Graves
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Cellular Response ◽  
Cell Damage ◽  
Cell Types ◽  
Biological Processes ◽  
Oxygen Species ◽  
Forkhead Transcription Factors ◽  
Foxo Transcription Factors

Diabetes is a chronic metabolic disorder, characterized by hyperglycemia resulting from insulin deficiency and/or insulin resistance. Recent evidence suggests that high levels of reactive oxygen species (ROS) and subsequent oxidative stress are key contributors in the development of diabetic complications. The FOXO family of forkhead transcription factors including FOXO1, FOXO3, FOXO4, and FOXO6 play important roles in the regulation of many cellular and biological processes and are critical regulators of cellular oxidative stress response pathways. FOXO1 transcription factors can affect a number of different tissues including liver, retina, bone, and cell types ranging from hepatocytes to microvascular endothelial cells and pericytes to osteoblasts. They are induced by oxidative stress and contribute to ROS-induced cell damage and apoptosis. In this paper, we discuss the role of FOXO transcription factors in mediating oxidative stress-induced cellular response.

Abstract 248: Elamipretide Reverses Dysregulation of mRNA Expression Levels of FoxO Transcription Factors 1, 3a and 4 in Left Ventricular Myocardium of Dogs with Advanced Heart Failure

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Ramesh C Gupta ◽  
Vinita Singh-Gupta ◽  
Kefei Zhang ◽  
Jiang Xu ◽  
Hani N Sabbah
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Transcription Factors ◽  
Mrna Expression ◽  
Advanced Heart Failure ◽  
Mrna Levels ◽  
Cellular Functions ◽  
Chronic Therapy ◽  
Foxo Transcription Factors ◽  
Mrna Expression Levels

Background: FoxO (Forkhead box) family of transcription factors play important roles in regulating the expression of genes involved in physiologic cellular functions that include 1) cell proliferation and growth, 2) oxidative stress and DNA repair, 3) apoptosis and autophagy, 4) energy metabolism and 5) immune system function. Many components of all 5 cellular functions are abnormal in the failing heart. FoxO1, FoxO3, and FoxO4 are members of the FoxO family and are expressed in adult cardiomyocytes. We previously showed that elamipretide (ELAM), a novel mitochondria-targeting peptide, reverses many of the abnormalities of the above captioned cellular function in dogs with advanced heart failure (HF). Abnormalities of expression and/or phosphorylation of FoxO1, FoxO3a and FoxO4 have been described in HF. Objective: This study examined the effects of chronic therapy with ELAM on levels of mRNA expression of FoxO1, FoxO3a and FoxO4 in LV myocardium of dogs with coronary microembolization-induced HF (LV ejection fraction ~30%). Methods: LV tissue from 14 HF dogs randomized to 3 months monotherapy with subcutaneous injections of ELAM (0.5 mg/kg once daily, n=7) or no therapy at all (control, CON, n=7) and tissue from 6 normal (NL) dogs was used in the study. Using specific primers, mRNA levels of FoxO1, FoxO3a, and FoxO4 normalized to β-actin, an internal control, were measured using real-time PCR in isolated RNA from LV tissue. Results: There were no differences in the levels of β-actin among the 3 study groups. mRNA expression levels of FoxO1 and 3a were significantly decreased and FoxO4 increased in HF-CON dogs compared to NL dogs (0.16, 0.19, and 2.48 fold change from NL respectively, p<0.05). Treatment of HF dogs with ELAM restored the expression of all 3 FoxO transcription factors to near NL (0.53, 0.65, and 1.21 fold change from NL respectively, P<0.05 vs. CON). Conclusions: mRNA levels of FoxO1 and FoxO3a are reduced and that of FoxO4 is increased in LV myocardium of HF dogs. Chronic therapy with ELAM normalizes expression of all 3 FoxO transcription factors. This improvement in FoxO expression is consistent with the observed reduction of oxidative stress, apoptosis and cytokines and improved energy metabolism in HF dogs following chronic therapy with ELAM.

scholarly journals Oxidative Stress and Autophagy as Key Targets in Melanoma Cell Fate

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5791
Author(s):  
Elisabetta Catalani ◽  
Matteo Giovarelli ◽  
Silvia Zecchini ◽  
Cristiana Perrotta ◽  
Davide Cervia
Keyword(s):  
Oxidative Stress ◽  
Drug Resistance ◽  
Skin Cancer ◽  
Cell Fate ◽  
Cancer Biology ◽  
Cancer Death ◽  
Nitrogen Species ◽  
Fundamental Challenge ◽  
Catabolic Process

Melanoma originates from the malignant transformation of melanocytes and is one of the most aggressive forms of cancer. The recent approval of several drugs has increased the chance of survival although a significant subset of patients with metastatic melanoma do not show a long-lasting response to these treatments. The complex cross-talk between oxidative stress and the catabolic process autophagy seems to play a central role in all aspects of melanoma pathophysiology, from initiation to progression and metastasis, including drug resistance. However, determining the fine role of autophagy in cancer death and in response to redox disruption is still a fundamental challenge in order to advance both basic and translational aspects of this field. In order to summarize the interactions among reactive oxygen and nitrogen species, autophagy machinery and proliferation/growth/death/apoptosis/survival, we provide here a narrative review of the preclinical evidence for drugs/treatments that modulate oxidative stress and autophagy in melanoma cells. The significance and the potential for pharmacological targeting (also through multiple and combination approaches) of these two different events, which can contribute independently or simultaneously to the fate of melanoma, may help to define new processes and their interconnections underlying skin cancer biology and unravel new reliable approaches.

scholarly journals The emerging role of FOXO transcription factors in pancreatic β cells

2007 ◽  
Vol 193 (2) ◽  
pp. 195-207 ◽  
Author(s):  
Dominique A Glauser ◽  
Werner Schlegel
Keyword(s):  
Transcription Factors ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Cell Mass ◽  
Endocrine Function ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Foxo Transcription Factors

FOXO transcription factors critically control fundamental cellular processes, including metabolism, cell differentiation, cell cycle arrest, DNA repair, and other reactions to cellular stress. FOXO factors sense the balance between stimuli promoting growth and differentiation versus stress stimuli signaling damage. Integrated through the FOXO system, these divergent stimuli decide on cell fate, a choice between proliferation, differentiation, or apoptosis. In pancreatic β cells, most recent evidence highlights complex FOXO-dependent responses to glucose, insulin, or other growth factors, which include regulatory feedback. In the short term, FOXO-dependent mechanisms help β cells to accomplish their endocrine function, and may increase their resistance to oxidative stress due to transient hyperglycemia. In the long term, FOXO-dependent responses lead to the adaptation of β cell mass, conditioning the future ability of the organism to produce insulin and cope with changes in fuel abundance. FOXO emerges as a key factor for the maintenance of a functional endocrine pancreas and represents an interesting element in the development of therapeutic approaches to treat diabetes. This review on the role of FOXO transcription factors in pancreatic β cells has three parts. In Part I, FOXO transcription factors will be presented in general: structure, molecular mechanisms of regulation, cellular functions, and physiological roles. Part II will focus on specific data about FOXO factors in pancreatic β cells. Lastly in Part III, it will be attempted to combine general and β cell-specific knowledge with the aim to envisage globally the role of FOXO factors in β cell-linked physiology and disease.

The role of Forkhead Box O 3a (FoxO3a) Transcription Factors in the Pathogenesis of Pulmonary Fibrosis

Pneumologie ◽  
2012 ◽  
Vol 66 (06) ◽  
Author(s):  
HM Al-Tamari ◽  
M Eschenhagen ◽  
A Schmall ◽  
R Savai ◽  
HA Ghofrani ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Pulmonary Fibrosis ◽  
Forkhead Box

scholarly journals Antioxidants in Fish Sperm and the Potential Role of Melatonin

Antioxidants ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 36
Author(s):  
Francisca Félix ◽  
Catarina C. V. Oliveira ◽  
Elsa Cabrita
Keyword(s):  
Oxidative Stress ◽  
Fish Cell ◽  
Cell Protection ◽  
Factors Affecting ◽  
Fish Sperm ◽  
Scavenger Activity ◽  
Stress Damage ◽  
Novel Antioxidants ◽  
Aquaculture Production

In recent years, the effects of novel antioxidants have played an important role in the research focusing on fish cell protection. As food demand grows, aquaculture production becomes more intensive, and fish are more exposed to oxidative stress conditions, like high densities, temperature shifting, frequent fish handling and samplings, and prophylactic or disease treatments, which expose fish to a different environment. Particularly in reproduction, germ cells lose antioxidant capacity with spermatogenesis, as spermatozoa are more prone to oxidative stress. Antioxidants have been used in a variety of fish physiological problems including in reproduction and in the establishment of cryopreservation protocols. From the most used antioxidants to natural plant food and herbs, and endogenously produced antioxidants, like melatonin, a review of the literature available in terms of their effects on the protection of fish spermatozoa is presented here in a classified structure. Several direct and indirect approaches to improve gamete quality using antioxidants administration are mentioned (through feed supplementation or by adding in cryopreservation media), as well as factors affecting the efficiency of these molecules and their mechanisms of action. Special attention is given to the unclear melatonin pathway and its potential scavenger activity to prevent and counteract oxidative stress damage on fish spermatozoa.

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