scholarly journals FoxO proteins: cunning concepts and considerations for the cardiovascular system

2009 ◽  
Vol 116 (3) ◽  
pp. 191-203 ◽  
Author(s):  
Kenneth Maiese ◽  
Zhao Zhong Chong ◽  
Yan Chen Shang ◽  
Jinling Hou

Dysfunction in the cardiovascular system can lead to the progression of a number of disease entities that can involve cancer, diabetes, cardiac ischaemia, neurodegeneration and immune system dysfunction. In order for new therapeutic avenues to overcome some of the limitations of present clinical treatments for these disorders, future investigations must focus upon novel cellular processes that control cellular development, proliferation, metabolism and inflammation. In this respect, members of the mammalian forkhead transcription factors of the O class (FoxOs) have increasingly become recognized as important and exciting targets for disorders of the cardiovascular system. In the present review, we describe the role of these transcription factors in the cardiovascular system during processes that involve angiogenesis, cardiovascular development, hypertension, cellular metabolism, oxidative stress, stem cell proliferation, immune system regulation and cancer. Current knowledge of FoxO protein function combined with future studies should continue to lay the foundation for the successful translation of these transcription factors into novel and robust clinical therapies.

2019 ◽  
Vol 20 (8) ◽  
pp. 799-816 ◽  
Author(s):  
Yue Qiu ◽  
Guo-wei Tu ◽  
Min-jie Ju ◽  
Cheng Yang ◽  
Zhe Luo

Sepsis, which is a highly heterogeneous syndrome, can result in death as a consequence of a systemic inflammatory response syndrome. The activation and regulation of the immune system play a key role in the initiation, development and prognosis of sepsis. Due to the different periods of sepsis when the objects investigated were incorporated, clinical trials often exhibit negative or even contrary results. Thus, in this review we aim to sort out the current knowledge in how immune cells play a role during sepsis.


2006 ◽  
Vol 397 (2) ◽  
pp. 233-246 ◽  
Author(s):  
Patrick J. E. C. Wijchers ◽  
J. Peter H. Burbach ◽  
Marten P. Smidt

Forkhead proteins comprise a highly conserved family of transcription factors, named after the original forkhead gene in Drosophila. To date, over 100 forkhead genes have been identified in a large variety of species, all sharing the evolutionary conserved ‘forkhead’ DNA-binding domain, and the cloning and characterization of forkhead genes have continued in recent years. Forkhead transcription factors regulate the expression of countless genes downstream of important signalling pathways in most, if not all, tissues and cell types. Recent work has provided novel insights into the mechanisms that contribute to their functional diversity, including functional protein domains and interactions of forkheads with other transcription factors. Studies using loss- and gain-of-function models have elucidated the role of forkhead factors in developmental biology and cellular functions such as metabolism, cell division and cell survival. The importance of forkhead transcription factors is underlined by the developmental defects observed in mutant model organisms, and multiple human disorders and cancers which can be attributed to mutations within members of the forkhead gene family. This review provides a comprehensive overview of current knowledge on forkhead transcription factors, from structural organization and regulatory mechanisms to cellular and developmental functions in mice and humans. Finally, we will discuss how novel insights gained from involvement of ‘Foxes’ in the mechanisms underlying human pathology may create new opportunities for treatment strategies.


2021 ◽  
Vol 1 (2) ◽  
Author(s):  
Esmaeil Mortaz ◽  
Neda K. Dezfuli

Context: The immunopathology of SARS-CoV-2 infection in COVID-19 is not well described yet, especially regarding dysregulation of the immune system. In this mini-review, current knowledge about the SARS-CoV-2 infection and immunopathogenesis of COVID-19 disease is described. We also discuss possible induced reactions against SARS-COV-2. Evidence Acquisition: Based on the authors' experience and knowledge, the current review aimed to, firstly, discuss and overview SRAS-CoV-2 infection and reactions in the body, and, secondly, to obtain related subjects from the PubMed database. Results and Conclusion: In most COVID-19 patients, uncontrollable cytokines secretion and mediators are major key points in the pathogenesis of the disease. Of all cytokines and mediators, serum levels of IL-6, IL-1β, TNF-α, IL-8, and soluble TNF-α receptor (sTNFR) have been reported. Lymphopenia and hypoxia, as well as the severity of the disease, can be considered as COVID-19 manifestations. High levels of intracellular NO inside of the red blood cells (RBCs) of patients drive the unexpected silent hypoxia phenotype induced ARDS importantly related to the patient's immune system dysfunction.


Author(s):  
F. Gabriella Fulcoli ◽  
Antonio Baldini

The two major cardiac cell lineages of the vertebrate heart, the first and second cardiac fields (FHF and SHF), have different developmental ontogeny and thus different transcription programs. Most remarkably, the fate of cardiac progenitors (CPs) of the FHF is restricted to cardiomyocyte differentiation. In contrast, SHF CPs, which are specified independently, are maintained in a multipotent state for a relatively longer developmental time and can differentiate into multiple cell types. The identity of the transcription factors and regulatory elements involved in progenitor cell programming and fate are only now beginning to emerge. Apparent inconsistencies between studies based on tissue culture and in vivo embryonic studies confirm that the ontogeny of cardiac progenitors is strongly driven or affected by regionalization, and thus by the signals that they receive in different regions. This chapter summarizes current knowledge about transcription factors and mechanisms driving CP ontogeny, with special focus on SHF development.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sara Forlani ◽  
Chiara Mizzotti ◽  
Simona Masiero

AbstractFruits and seeds resulting from fertilization of flowers, represent an incredible evolutionary advantage in angiosperms and have seen them become a critical element in our food supply.Many studies have been conducted to reveal how fruit matures while protecting growing seeds and ensuring their dispersal. As result, several transcription factors involved in fruit maturation and senescence have been isolated both in model and crop plants. These regulators modulate several cellular processes that occur during fruit ripening such as chlorophyll breakdown, tissue softening, carbohydrates and pigments accumulation.The NAC superfamily of transcription factors is known to be involved in almost all these aspects of fruit development and maturation. In this review, we summarise the current knowledge regarding NACs that modulate fruit ripening in model species (Arabidopsis thaliana and Solanum lycopersicum) and in crops of commercial interest (Oryza sativa, Malus domestica, Fragaria genus, Citrus sinensis and Musa acuminata).


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Matteo Barberis

AbstractNetworks of interacting molecules organize topology, amount, and timing of biological functions. Systems biology concepts required to pin down ‘network motifs’ or ‘design principles’ for time-dependent processes have been developed for the cell division cycle, through integration of predictive computer modeling with quantitative experimentation. A dynamic coordination of sequential waves of cyclin-dependent kinases (cyclin/Cdk) with the transcription factors network offers insights to investigate how incompatible processes are kept separate in time during the eukaryotic cell cycle. Here this coordination is discussed for the Forkhead transcription factors in light of missing gaps in the current knowledge of cell cycle control in budding yeast. An emergent design principle is proposed where cyclin waves are synchronized by a cyclin/Cdk-mediated feed-forward regulation through the Forkhead as a transcriptional timer. This design is rationalized by the bidirectional interaction between mitotic cyclins and the Forkhead transcriptional timer, resulting in an autonomous oscillator that may be instrumental for a well-timed progression throughout the cell cycle. The regulation centered around the cyclin/Cdk–Forkhead axis can be pivotal to timely coordinate cell cycle dynamics, thereby to actuate the quantitative model of Cdk control.


2005 ◽  
Vol 83 (4) ◽  
pp. 535-547 ◽  
Author(s):  
Gareth N Corry ◽  
D Alan Underhill

To date, the majority of the research regarding eukaryotic transcription factors has focused on characterizing their function primarily through in vitro methods. These studies have revealed that transcription factors are essentially modular structures, containing separate regions that participate in such activities as DNA binding, protein–protein interaction, and transcriptional activation or repression. To fully comprehend the behavior of a given transcription factor, however, these domains must be analyzed in the context of the entire protein, and in certain cases the context of a multiprotein complex. Furthermore, it must be appreciated that transcription factors function in the nucleus, where they must contend with a variety of factors, including the nuclear architecture, chromatin domains, chromosome territories, and cell-cycle-associated processes. Recent examinations of transcription factors in the nucleus have clarified the behavior of these proteins in vivo and have increased our understanding of how gene expression is regulated in eukaryotes. Here, we review the current knowledge regarding sequence-specific transcription factor compartmentalization within the nucleus and discuss its impact on the regulation of such processes as activation or repression of gene expression and interaction with coregulatory factors.Key words: transcription, subnuclear localization, chromatin, gene expression, nuclear architecture.


Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1287
Author(s):  
T. Walter ◽  
Jennifer Iudicello ◽  
Debra Cookson ◽  
Donald Franklin ◽  
Bin Tang ◽  
...  

Methamphetamine (METH) use disorder is highly prevalent among people with HIV (PWH) and is a significant public health problem. HIV and METH use are each associated with immune system dysfunction; however, the combined effects on the immune system are poorly understood. This cross-sectional project measured soluble immune biomarkers in plasma and cerebrospinal fluid (CSF) collected from a control group, people with a history of a METH use disorder (METH+), PWH with no history of METH use disorder (HIV+), and PWH with a history of METH use disorder (HIV+/METH+). HIV, METH, and immune dysfunction can also be associated with affective and cognitive deficits, so we characterized mood and cognition in our participants. Two factor analyses were performed for the plasma and CSF biomarkers. Plasma IL-8, Ccl2, VEGF, and 8-isoprostane loaded onto one factor that was highest in the HIV+/METH+ group (p < 0.047) reflecting worse inflammation, vascular injury, and oxidative stress. This plasma factor was also negatively correlated with delayed recall (R = −0.49, p = 0.010), which was worst in the HIV+/METH+ group (p = 0.030 compared to the control group). Overall, these data implicate that combined HIV-1 infection and METH use may exacerbate inflammation, leading to worse cognition.


Sign in / Sign up

Export Citation Format

Share Document