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.

scholarly journals Tryptophan-kynurenine pathway as a novel link between gut microbiota and schizophrenia: A review

2021 ◽  
Vol 18 (4) ◽  
pp. 897-905
Author(s):  
Yaping Wang ◽  
Xiuxia Yuan ◽  
Yulin Kang ◽  
Xueqin Song
Keyword(s):  
Oxidative Stress ◽  
Gut Microbiota ◽  
Neuronal Excitability ◽  
Kynurenine Pathway ◽  
Inflammatory Factors ◽  
Biological Processes ◽  
Oxygen Species ◽  
Tryptophan Catabolism ◽  
And Oxidative Stress

Gut microbiota and its metabolite tryptophan play an important role in regulating neurotransmission, immune homeostasis and oxidative stress which are critical for brain development. The kynurenine pathway is the main route of tryptophan catabolism. Kynurenine metabolites regulate many biological processes including host-microbiome communication, immunity and oxidative stress, as well as neuronal excitability. The accumulation of metabolites produced by kynurenine pathway in brain results in the activation of the immune system (increase in the levels of inflammatory factors) and oxidative stress (production of reactive oxygen species, ROS), which are associated with mental disorders, for example schizophrenia. Thus, it was hypothesized that perturbations in kynurenine pathway could cause activation of immunity, and that oxidative stress may be involved in the etiology of schizophrenia. The present work is a review of the latest studies on the possible role of kynurenine pathway in schizophrenia, and mechanism(s) involved.

FoxO3 transcription factor promotes autophagy after oxidative stress injury in HT22 cells

2020 ◽  
Author(s):  
Aiqing Deng ◽  
Limin Ma ◽  
Xueli Zhou ◽  
Xin Wang ◽  
Shouyan Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Cell Injury ◽  
Cell Damage ◽  
Critical Role ◽  
Neuronal Cell ◽  
Ht22 Cells ◽  
Stress Injury ◽  
Oxidative Stress Injury

Autophagy has been implicated in neurodegenerative diseases. Forkhead box O3 (FoxO3) transcription factors promote autophagy in heart and inhibit oxidative damage. Here we investigate the role of FoxO3 transcription factors in regulating autophagy after oxidative stress injury in immortalized mouse hippocampal cell line (HT22). The present study confirms that hydrogen peroxide (H2O2) injury could induce autophagy and FoxO3 activation in HT22 cells. In addition, overexpression of FoxO3 enhanced H2O2-induced autophagy activation and suppressed neuronal cell damage, while knockdown of FoxO3 reduced H2O2-induced autophagy activation and exacerbated neuronal cell injury. Inhibition of autophagy by 3-Methyladenine (3-MA) resulted in reduced cell viability, increased production of reactive oxygen species (ROS), promoted nuclear condensation and decreased expression of antiapoptotic and autophagy-related proteins, indicating that autophagy may have protective effects on H2O2-induced injury in HT22 cells. Moreover, overexpression of FoxO3 prevented exacerbation of brain damage induced by 3-MA. Taken together, these results show that activation of FoxO3 could induce autophagy and inhibit H2O2-induced damage in HT22 cells. Our study demonstrates the critical role of FoxO3 in regulating autophagy in brain.

scholarly journals FOXO Transcription Factors: Their Clinical Significance and Regulation

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Yu Wang ◽  
Yanmin Zhou ◽  
Dana T. Graves
Keyword(s):  
Transcription Factors ◽  
Cellular Proliferation ◽  
Cell Types ◽  
Mitogen Activated Protein Kinase ◽  
Survival Pathways ◽  
Mitogen Activated Protein ◽  
Foxo Transcription Factors ◽  
Phosphoinositide 3 Kinase ◽  
Clinical Conditions

Members of the class O of forkhead box transcription factors (FOXO) have important roles in metabolism, cellular proliferation, stress resistance, and apoptosis. The activity of FOXOs is tightly regulated by posttranslational modification, including phosphorylation, acetylation, and ubiquitylation. Activation of cell survival pathways such as phosphoinositide-3-kinase/AKT/IKK or RAS/mitogen-activated protein kinase phosphorylates FOXOs at different sites which regulate FOXOs nuclear localization or degradation. FOXO transcription factors are upregulated in a number of cell types including hepatocytes, fibroblasts, osteoblasts, keratinocytes, endothelial cells, pericytes, and cardiac myocytes. They are involved in a number of pathologic and physiologic processes that include proliferation, apoptosis, autophagy, metabolism, inflammation, cytokine expression, immunity, differentiation, and resistance to oxidative stress. These processes impact a number of clinical conditions such as carcinogenesis, diabetes, diabetic complications, cardiovascular disease, host response, and wound healing. In this paper, we focus on the potential role of FOXOs in different disease models and the regulation of FOXOs by various stimuli.

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.

scholarly journals Role of Melanin in Melanocyte Dysregulation of Reactive Oxygen Species

2013 ◽  
Vol 2013 ◽  
pp. 1-3 ◽  
Author(s):  
Noah C. Jenkins ◽  
Douglas Grossman
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Cell Types ◽  
Oxygen Species ◽  
Intracellular Ros ◽  
Potential Alternative ◽  
Oxidative Insult ◽  
Increased Susceptibility

We have recently reported a potential alternative tumor suppressor function for p16 relating to its capacity to regulate oxidative stress and observed that oxidative dysregulation in p16-depleted cells was most profound in melanocytes, compared to keratinocytes or fibroblasts. Moreover, in the absence of p16 depletion or exogenous oxidative insult, melanocytes exhibited significantly higher basal levels of reactive oxygen species (ROS) than these other epidermal cell types. Given the role of oxidative stress in melanoma development, we speculated that this increased susceptibility of melanocytes to oxidative stress (and greater reliance on p16 for suppression of ROS) may explain why genetic compromise of p16 is more commonly associated with predisposition to melanoma rather than other cancers. Here we show that the presence of melanin accounts for this differential oxidative stress in normal and p16-depleted melanocytes. Thus the presence of melanin in the skin appears to be a double-edged sword: it protects melanocytes as well as neighboring keratinocytes in the skin through its capacity to absorb UV radiation, but its synthesis in melanocytes results in higher levels of intracellular ROS that may increase melanoma susceptibility.

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 The “Janus” Role of C/EBPs Family Members in Cancer Progression

2020 ◽  
Vol 21 (12) ◽  
pp. 4308 ◽  
Author(s):  
Manlio Tolomeo ◽  
Stefania Grimaudo
Keyword(s):  
Transcription Factors ◽  
Cancer Progression ◽  
Tumor Suppressors ◽  
Cellular Response ◽  
Cellular Proliferation ◽  
Cell Types ◽  
Tumor Promoters ◽  
Expression Of Genes ◽  
Molecular Aspects

CCAAT/enhancer-binding proteins (C/EBPs) constitute a family of transcription factors composed of six members that are critical for normal cellular differentiation in a variety of tissues. They promote the expression of genes through interaction with their promoters. Moreover, they have a key role in regulating cellular proliferation through interaction with cell cycle proteins. C/EBPs are considered to be tumor suppressor factors due to their ability to arrest cell growth (contributing to the terminal differentiation of several cell types) and for their role in cellular response to DNA damage, nutrient deprivation, hypoxia, and genotoxic agents. However, C/EBPs can elicit completely opposite effects on cell proliferation and cancer development and they have been described as both tumor promoters and tumor suppressors. This “Janus” role of C/EBPs depends on different factors, such as the type of tumor, the isoform/s expressed in cells, the type of dimerization (homo- or heterodimerization), the presence of inhibitory elements, and the ability to inhibit the expression of other tumor suppressors. In this review, we discuss the implication of the C/EBPs family in cancer, focusing on the molecular aspects that make these transcription factors tumor promoters or tumor suppressors.

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 Transcription Factors: Regulators of Metabolism and Stress Resistance

Proceedings ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 11
Author(s):  
Klotz
Keyword(s):  
Transcription Factors ◽  
Stress Resistance ◽  
Mammalian Cells ◽  
Cellular Response ◽  
Target Genes ◽  
Model Organism ◽  
Genes Encoding ◽  
Antioxidant Proteins ◽  
Foxo Transcription Factors

FOXO (Forkhead box, class O) proteins are transcriptional regulators ubiquitously expressed in mammalian cells with roles in modulating fuel metabolism, stress resistance and cell death. FOXO transcription factors are regulated by redox processes at several levels, including enzymatic and nonenzymatic posttranslational modification. Target genes controlled by FOXO proteins include genes encoding antioxidant proteins, thus likely contributing to the key role FOXOs play in the cellular response to oxidative stress. Here, an overview is provided on (i) the modulation of FOXO proteins by thiol depleting agents, (ii) consequences of thiol depletion for stress resistance and life span of a model organism, Caenorhabditis elegans and (iii) the role of FOXO proteins therein.

scholarly journals The Role of Oxidative Stress in Hyperuricemia and Xanthine Oxidoreductase (XOR) Inhibitors

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Ning Liu ◽  
Hu Xu ◽  
Qianqian Sun ◽  
Xiaojuan Yu ◽  
Wentong Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Metabolic Disease ◽  
Uric Acid ◽  
Drug Target ◽  
Cell Damage ◽  
Etiologic Factor ◽  
Xanthine Oxidoreductase ◽  
Oxygen Species ◽  
Acid Transport

Uric acid is the end product of purine metabolism in humans. Hyperuricemia is a metabolic disease caused by the increased formation or reduced excretion of serum uric acid (SUA). Alterations in SUA homeostasis have been linked to a number of diseases, and hyperuricemia is the major etiologic factor of gout and has been correlated with metabolic syndrome, cardiovascular disease, diabetes, hypertension, and renal disease. Oxidative stress is usually defined as an imbalance between free radicals and antioxidants in our body and is considered to be one of the main causes of cell damage and the development of disease. Studies have demonstrated that hyperuricemia is closely related to the generation of reactive oxygen species (ROS). In the human body, xanthine oxidoreductase (XOR) catalyzes the oxidative hydroxylation of hypoxanthine to xanthine to uric acid, with the accompanying production of ROS. Therefore, XOR is considered a drug target for the treatment of hyperuricemia and gout. In this review, we discuss the mechanisms of uric acid transport and the development of hyperuricemia, emphasizing the role of oxidative stress in the occurrence and development of hyperuricemia. We also summarize recent advances and new discoveries in XOR inhibitors.

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