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.

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.

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 Regulation of the p75 neurotrophin receptor attenuates neuroinflammation and stimulates hippocampal neurogenesis in experimental Streptococcus pneumoniae meningitis

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Dandan Zhang ◽  
Shengnan Zhao ◽  
Zhijie Zhang ◽  
Danfeng Xu ◽  
Di Lian ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Streptococcus Pneumoniae ◽  
Proinflammatory Cytokines ◽  
Neuronal Apoptosis ◽  
Hippocampal Neurogenesis ◽  
Clinical Severity ◽  
Neurotrophin Receptor ◽  
Apoptosis And Necrosis

Abstract Background Streptococcus pneumoniae meningitis is a destructive central nervous system (CNS) infection with acute and long-term neurological disorders. Previous studies suggest that p75NTR signaling influences cell survival, apoptosis, and proliferation in brain-injured conditions. However, the role of p75NTR signaling in regulating pneumococcal meningitis (PM)-induced neuroinflammation and altered neurogenesis remains largely to be elucidated. Methods p75NTR signaling activation in the pathological process of PM was assessed. During acute PM, a small-molecule p75NTR modulator LM11A-31 or vehicle was intranasally administered for 3 days prior to S. pneumoniae exposure. At 24 h post-infection, clinical severity, histopathology, astrocytes/microglia activation, neuronal apoptosis and necrosis, inflammation-related transcription factors and proinflammatory cytokines/mediators were evaluated. Additionally, p75NTR was knocked down by the adenovirus-mediated short-hairpin RNA (shRNA) to ascertain the role of p75NTR in PM. During long-term PM, the intranasal administration of LM11A-31 or vehicle was continued for 7 days after successfully establishing the PM model. Dynamic changes in inflammation and hippocampal neurogenesis were assessed. Results Our results revealed that both 24 h (acute) and 7, 14, 28 day (long-term) groups of infected rats showed increased p75NTR expression in the brain. During acute PM, modulation of p75NTR through pretreatment of PM model with LM11A-31 significantly alleviated S. pneumoniae-induced clinical severity, histopathological injury and the activation of astrocytes and microglia. LM11A-31 pretreatment also significantly ameliorated neuronal apoptosis and necrosis. Moreover, we found that blocking p75NTR with LM11A-31 decreased the expression of inflammation-related transcription factors (NF-κBp65, C/EBPβ) and proinflammatory cytokines/mediators (IL-1β, TNF-α, IL-6 and iNOS). Furthermore, p75NTR knockdown induced significant changes in histopathology and inflammation-related transcription factors expression. Importantly, long-term LM11A-31 treatment accelerated the resolution of PM-induced inflammation and significantly improved hippocampal neurogenesis. Conclusion Our findings suggest that the p75NTR signaling plays an essential role in the pathogenesis of PM. Targeting p75NTR has beneficial effects on PM rats by alleviating neuroinflammation and promoting hippocampal neurogenesis. Thus, the p75NTR signaling may be a potential therapeutic target to improve the outcome of PM.

scholarly journals Etiology of differentiated carcinoma of the thyroid current apprehension

2003 ◽  
Vol 50 (3) ◽  
pp. 51-55
Author(s):  
Ruben Han
Keyword(s):  
Animal Experiments ◽  
Growth Control ◽  
Significant Risk ◽  
Ionising Radiation ◽  
Sodium Iodide Symporter ◽  
Chemical Agents ◽  
Tsh Secretion ◽  
Genetic And Environmental Factors

It is apparent that in the last decade carcinoma of the thyroid is becoming increasingly prevalent. The multistage complex theory of thyroid carcinogenesis is based on observations made on cohort patients studies and during animal experiments over a period of last fifty years. The process of thyroid oncogenesis is conceived to be a series of events induced by genetic and environmental factors which alter follicular cells division and growth control. These factors can be considered as initiators (chemical agents and ionising radiation) and promoters (some goitrogenes and drugs). The first class of factors induce incipient tumorigenesis while the second augments TSH secretion and radically increases tumour growth. Normally silent, intracellular proto-oncogenes (of which Ret/PTC series are the most conceived ones) can become activated by chromosomal translocations, deletions or mutations and can transform normal follicular cell into a condition of uncontrolled division and growth. The most significant known cause of thyroid carcinomas in men is exposure to external or internal ionising radiation. Beside that, long-term iodine deficiency, effects of certain chemical carcinogens, drugs and goitrogenes must be considered as significant risk factors. Possible role of sodium/iodide symporter is becoming an objective of the most recent investigations.

scholarly journals Regulation of the p75 Neurotrophin Receptor Attenuates Neuroinflammation and Stimulates Hippocampal Neurogenesis in Experimental Streptococcus Pneumoniae Meningitis

2021 ◽  
Author(s):  
Dandan Zhang ◽  
Shengnan Zhao ◽  
Zhijie Zhang ◽  
Danfeng Xu ◽  
Di Lian ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Streptococcus Pneumoniae ◽  
Cell Apoptosis ◽  
Neuronal Cell ◽  
Hippocampal Neurogenesis ◽  
Clinical Severity ◽  
Neurotrophin Receptor ◽  
Double Labeling

Abstract Background: Streptococcus pneumoniae meningitis is a destructive central nervous system (CNS) infection with acute and long-term neurological disorders. Compelling evidence provided by previous studies suggests that p75NTR signaling influences cell survival, apoptosis, and proliferation in brain-injured conditions. However, the role of p75NTR signaling in regulating pneumococcal meningitis (PM)-induced neuroinflammation and altered neurogenesis remains largely to be elucidated.Methods: p75NTR signaling activation in the pathological process of PM was assessed. During acute PM, a small-molecule p75NTR modulator LM11A-31 or vehicle was intranasally administered for 3 days prior to S.pneumoniae exposure. At 24h post-infection, clinical severity, histopathology, astrocytes/microglia activation, neuronal cell apoptosis and death, inflammation-related transcription factors and inflammatory factors were evaluated. Additionally, p75NTR was knocked down by the adenovirus-mediated short-hairpin RNA (shRNA) to ascertain the role of p75NTR in PM. During long-term PM, the intranasal administration of LM11A-31 or vehicle was continued for 7 days after successfully establishing the PM model. Hippocampal neurogenesis was evaluated by double-labeling immunofluorescence with EdU, DCX and NeuN. Results: Our results revealed that both 24h (acute) and 7,14,28day (long-term) groups of infected rats demonstrated increased p75NTR expression in the brain. During acute PM, modulation of p75NTR through pretreatment of PM model with LM11A-31 significantly alleviated S.pneumoniae-induced clinical severity, histopathological injury and the activation of astrocytes and microglia. LM11A-31 pretreatment also significantly ameliorated neuronal cell apoptosis and death. Moreover, we found that blocking p75NTR with LM11A-31 decreased the expression of inflammation-related transcription factors (NF-κBp65, C/EBPβ) and proinflammatory cytokine (IL-1β, TNF-α, IL-6 and iNOS) in the cortex and hippocampus. Furthermore, p75NTR knockdown induced significant changes in histopathology and inflammation-related transcription factors expression. Importantly, combined LM11A-31 adjuvant therapy significantly improved hippocampal neurogenesis.Conclusion: Our findings suggest that the p75NTR signaling plays an essential role in the pathogenesis of PM. Targeting p75NTR has benefit effects on PM rats by alleviating neuroinflammation and promoting hippocampal neurogenesis. Thus, the p75NTR signaling may be a potential therapeutic target to improve the outcome of PM.

scholarly journals Highly Specialized Role of Forkhead Box O Transcription Factors in the Immune System

2011 ◽  
Vol 14 (4) ◽  
pp. 663-674 ◽  
Author(s):  
Anne S. Dejean ◽  
Stephen M. Hedrick ◽  
Yann M. Kerdiles
Keyword(s):  
Transcription Factors ◽  
Immune System ◽  
Forkhead Box

scholarly journals Signaling Network of Forkhead Family of Transcription Factors (FOXO) in Dietary Restriction

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 100 ◽  
Author(s):  
Yizhou Jiang ◽  
Fengxia Yan ◽  
Zhongping Feng ◽  
Philip Lazarovici ◽  
Wenhua Zheng
Keyword(s):  
Transcription Factors ◽  
Dietary Restriction ◽  
Molecular Mechanisms ◽  
Mammalian Target Of Rapamycin ◽  
Redox Balance ◽  
Energy Restriction ◽  
Health Span ◽  
Forkhead Box ◽  
Amp Activated Protein Kinase

Dietary restriction (DR), which is defined as a reduction of particular or total nutrient intake without causing malnutrition, has been proved to be a robust way to extend both lifespan and health-span in various species from yeast to mammal. However, the molecular mechanisms by which DR confers benefits on longevity were not yet fully elucidated. The forkhead box O transcription factors (FOXOs), identified as downstream regulators of the insulin/IGF-1 signaling pathway, control the expression of many genes regulating crucial biological processes such as metabolic homeostasis, redox balance, stress response and cell viability and proliferation. The activity of FOXOs is also mediated by AMP-activated protein kinase (AMPK), sirtuins and the mammalian target of rapamycin (mTOR). Therefore, the FOXO-related pathways form a complex network critical for coordinating a response to environmental fluctuations in order to maintain cellular homeostasis and to support physiological aging. In this review, we will focus on the role of FOXOs in different DR interventions. As different DR regimens or calorie (energy) restriction mimetics (CRMs) can elicit both distinct and overlapped DR-related signaling pathways, the benefits of DR may be maximized by combining diverse forms of interventions. In addition, a better understanding of the precise role of FOXOs in different mechanistic aspects of DR response would provide clear cellular and molecular insights on DR-induced increase of lifespan and health-span.

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