scholarly journals Enhanced expression and activation of pro-inflammatory transcription factors distinguish aneurysmal from atherosclerotic aorta: IL-6- and IL-8-dominated inflammatory responses prevail in the human aneurysm

2008 ◽  
Vol 114 (11) ◽  
pp. 687-697 ◽  
Author(s):  
Jan H. N. Lindeman ◽  
Hazem Abdul-Hussien ◽  
Alexander F. M. Schaapherder ◽  
J. Hajo VAN Bockel ◽  
Jan H. VON DER Thüsen ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Cellular Response ◽  
Target Genes ◽  
Inflammatory Responses ◽  
Interleukin 2 ◽  
Cellular Responses ◽  
Vasa Vasorum ◽  
Inflammatory Factors ◽  
Inflammatory Parameters ◽  
Enhanced Expression

Inflammation plays a key role in the pathogenesis of an AAA (abdominal aortic aneurysm); however, the nature of the inflammatory factors and cellular response(s) involved in AAA growth is controversial. In the present study, we set out to determine the aortic levels of inflammatory cytokines in relation to downstream inflammatory transcription factors and cellular responses. A comparison of AAA wall samples with atherosclerotic wall samples taken from the same aortic region allowed AAA-specific inflammatory parameters to be identified that distinguish AAAs from ASD (aortic atherosclerotic disease). RT-PCR (real-time PCR), ELISA, Western blotting and immunohistochemistry were combined to assess cytokines and transcription factors at the mRNA and protein level, and their activation status. Compared with ASD, inflammatory parameters associated with Th1-type [T-bet, IL (interleukin)-2, IFN-γ (interferon-γ), TNF-α (tumour necrosis factor-α), IL-1α and cytotoxic T-cells] and Th2-type [GATA3, IL-4, IL-10, IL-13 and B-cells] responses were all increased in AAA samples. Evaluation of major downstream inflammatory transcription factors revealed higher baseline levels of C/EBP (CCAAT/enhancer-binding protein) α, β and δ in the AAA samples. Baseline p65 NF-κB (nuclear factor κB) and c-Jun [AP-1 (activator protein-1)] levels were comparable, but their activated forms were strongly increased in the AAA samples. Downstream target genes of p65 NF-κB, c-Jun, IL-6 and IL-8 were hyperexpressed. Molecular and cellular processes associated with IL-6 and IL-8 hyperactivation were enhanced in the AAA samples, i.e. the expression of phospho-STAT-3 (signal transducer and activator of transcription-3) and perforin were elevated, and the content of plasma cells, neutrophils and vasa vasorum was increased. In conclusion, our findings demonstrate that an AAA is a general inflammatory condition which is characterized by enhanced expression and activation of pro-inflammatory transcription factors, accompanied by IL-6 and IL-8 hyperexpression and exaggerated downstream cellular responses, which together clearly distinguish an AAA from ASD.

scholarly journals Inflammatory responses to secondary organic aerosols (SOA) generated from biogenic and anthropogenic precursors

2017 ◽  
Vol 17 (18) ◽  
pp. 11423-11440 ◽  
Author(s):  
Wing Y. Tuet ◽  
Yunle Chen ◽  
Shierly Fok ◽  
Julie A. Champion ◽  
Nga L. Ng
Keyword(s):  
Cellular Response ◽  
Secondary Organic Aerosols ◽  
Inflammatory Responses ◽  
Organic Aerosols ◽  
Cellular Responses ◽  
Carbon Chain ◽  
Formation Condition ◽  
Carbon Chain Length ◽  
Health Implications ◽  
Tnf Α

Abstract. Cardiopulmonary health implications resulting from exposure to secondary organic aerosols (SOA), which comprise a significant fraction of ambient particulate matter (PM), have received increasing interest in recent years. In this study, alveolar macrophages were exposed to SOA generated from the photooxidation of biogenic and anthropogenic precursors (isoprene, α-pinene, β-caryophyllene, pentadecane, m-xylene, and naphthalene) under different formation conditions (RO2 + HO2 vs. RO2 + NO dominant, dry vs. humid). Various cellular responses were measured, including reactive oxygen and nitrogen species (ROS/RNS) production and secreted levels of cytokines, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). SOA precursor identity and formation condition affected all measured responses in a hydrocarbon-specific manner. With the exception of naphthalene SOA, cellular responses followed a trend where TNF-α levels reached a plateau with increasing IL-6 levels. ROS/RNS levels were consistent with relative levels of TNF-α and IL-6, due to their respective inflammatory and anti-inflammatory effects. Exposure to naphthalene SOA, whose aromatic-ring-containing products may trigger different cellular pathways, induced higher levels of TNF-α and ROS/RNS than suggested by the trend. Distinct cellular response patterns were identified for hydrocarbons whose photooxidation products shared similar chemical functionalities and structures, which suggests that the chemical structure (carbon chain length and functionalities) of photooxidation products may be important for determining cellular effects. A positive nonlinear correlation was also detected between ROS/RNS levels and previously measured DTT (dithiothreitol) activities for SOA samples. In the context of ambient samples collected during summer and winter in the greater Atlanta area, all laboratory-generated SOA produced similar or higher levels of ROS/RNS and DTT activities. These results suggest that the health effects of SOA are important considerations for understanding the health implications of ambient aerosols.

scholarly journals Unification of Opposites between Two Antioxidant Transcription Factors Nrf1 and Nrf2 in Mediating Distinct Cellular Responses to the Endoplasmic Reticulum Stressor Tunicamycin

Antioxidants ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 4 ◽  
Author(s):  
Yu-ping Zhu ◽  
Ze Zheng ◽  
Shaofan Hu ◽  
Xufang Ru ◽  
Zhuo Fan ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Er Stress ◽  
Target Genes ◽  
Cellular Responses ◽  
Water Soluble ◽  
Heme Oxygenase 1 ◽  
Nuclear Factor ◽  
Activating Transcription Factor

The water-soluble Nrf2 (nuclear factor, erythroid 2-like 2, also called Nfe2l2) is accepted as a master regulator of antioxidant responses to cellular stress, and it was also identified as a direct target of the endoplasmic reticulum (ER)-anchored PERK (protein kinase RNA-like endoplasmic reticulum kinase). However, the membrane-bound Nrf1 (nuclear factor, erythroid 2-like 1, also called Nfe2l1) response to ER stress remains elusive. Herein, we report a unity of opposites between these two antioxidant transcription factors, Nrf1 and Nrf2, in coordinating distinct cellular responses to the ER stressor tunicamycin (TU). The TU-inducible transcription of Nrf1 and Nrf2, as well as GCLM (glutamate cysteine ligase modifier subunit) and HO-1 (heme oxygenase 1), was accompanied by activation of ER stress signaling networks. Notably, the unfolded protein response (UPR) mediated by ATF6 (activating transcription factor 6), IRE1 (inositol requiring enzyme 1) and PERK was significantly suppressed by Nrf1α-specific knockout, but hyper-expression of Nrf2 and its target genes GCLM and HO-1 has retained in Nrf1α−/− cells. By contrast, Nrf2−/−ΔTA cells with genomic deletion of its transactivation (TA) domain resulted in significant decreases of GCLM, HO-1 and Nrf1; this was accompanied by partial decreases of IRE1 and ATF6, rather than PERK, but with an increase of ATF4 (activating transcription factor 4). Interestingly, Nrf1 glycosylation and its trans-activity to mediate the transcriptional expression of the 26S proteasomal subunits, were repressed by TU. This inhibitory effect was enhanced by Nrf1α−/− and Nrf2−/−ΔTA, but not by a constitutive activator caNrf2ΔN (that increased abundances of the non-glycosylated and processed Nrf1). Furthermore, caNrf2ΔN also enhanced induction of PERK and IRE1 by TU, but reduced expression of ATF4 and HO-1. Thus, it is inferred that such distinct roles of Nrf1 and Nrf2 are unified to maintain cell homeostasis by a series of coordinated ER-to-nuclear signaling responses to TU. Nrf1α (i.e., a full-length form) acts in a cell-autonomous manner to determine the transcription of most of UPR-target genes, albeit Nrf2 is also partially involved in this process. Consistently, transactivation of ARE (antioxidant response element)-driven BIP (binding immunoglobulin protein)-, PERK- and XBP1 (X-box binding protein 1)-Luc reporter genes was mediated directly by Nrf1 and/or Nrf2. Interestingly, Nrf1α is more potent than Nrf2 at mediating the cytoprotective responses against the cytotoxicity of TU alone or plus tBHQ (tert-butylhydroquinone). This is also further supported by the evidence that the intracellular reactive oxygen species (ROS) levels are increased in Nrf1α−/− cells, but rather are, to our surprise, decreased in Nrf2−/−ΔTA cells.

scholarly journals Differential Contribution of N- and C-Terminal Regions of HIF1α and HIF2α to Their Target Gene Selectivity

2020 ◽  
Vol 21 (24) ◽  
pp. 9401
Author(s):  
Antonio Bouthelier ◽  
Florinda Meléndez-Rodríguez ◽  
Andrés A. Urrutia ◽  
Julián Aragonés
Keyword(s):  
Transcription Factors ◽  
Dna Binding ◽  
Cellular Response ◽  
Target Gene ◽  
Target Genes ◽  
Transactivation Domain ◽  
Transactivation Domains ◽  
Relative Contribution

Cellular response to hypoxia is controlled by the hypoxia-inducible transcription factors HIF1α and HIF2α. Some genes are preferentially induced by HIF1α or HIF2α, as has been explored in some cell models and for particular sets of genes. Here we have extended this analysis to other HIF-dependent genes using in vitro WT8 renal carcinoma cells and in vivo conditional Vhl-deficient mice models. Moreover, we generated chimeric HIF1/2 transcription factors to study the contribution of the HIF1α and HIF2α DNA binding/heterodimerization and transactivation domains to HIF target specificity. We show that the induction of HIF1α-dependent genes in WT8 cells, such as CAIX (CAR9) and BNIP3, requires both halves of HIF, whereas the HIF2α transactivation domain is more relevant for the induction of HIF2 target genes like the amino acid carrier SLC7A5. The HIF selectivity for some genes in WT8 cells is conserved in Vhl-deficient lung and liver tissue, whereas other genes like Glut1 (Slc2a1) behave distinctly in these tissues. Therefore the relative contribution of the DNA binding/heterodimerization and transactivation domains for HIF target selectivity can be different when comparing HIF1α or HIF2α isoforms, and that HIF target gene specificity is conserved in human and mouse cells for some of the genes analyzed.

scholarly journals Transcriptome Analysis of The Inflammatory Responses of Bovine Mammary Epithelial Cells: Exploring Immunomodulatory Target Genes for Bovine Mastitis

Pathogens ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 200 ◽  
Author(s):  
Md. Aminul Islam ◽  
Michihiro Takagi ◽  
Kohtaro Fukuyama ◽  
Ryoya Komatsu ◽  
Leonardo Albarracin ◽  
...  
Keyword(s):  
Dairy Cows ◽  
Bacterial Infections ◽  
Target Genes ◽  
Inflammatory Responses ◽  
Bovine Mastitis ◽  
Immune Defense ◽  
Mammary Epithelial ◽  
Inflammatory Factors ◽  
Cytokines And Chemokines

Bovine mastitis is the inflammatory reaction of the mammary gland and is commonly caused by bacterial infections in high-yielding dairy cows. The detailed investigation of the immunotranscriptomic response of bovine mammary epithelial (BME) cells to pattern recognition receptors (PRRs) activation by microbial-associated molecular patterns (MAMPs) can be of great importance for understanding the innate immune defense mechanisms, and for exploring the immunomodulatory candidate genes. In this work, we investigated the transcriptome modifications of BME cells after the in vitro stimulation with Escherichia coli derived lipopolysaccharide (LPS) and heat-killed Staphylococcus aureus JE2 and S. aureus SA003. In addition, the effect of Pam3CSK4 (a synthetic triacylated lipopeptide that activates Toll-like receptor 2 (TLR2)), and the intracellular chemotactic protein cyclophilin A (CyPA), which is secreted by BME cells during mastitis, in the expression changes of selected cytokines and chemokines were evaluated by qPCR. Microarray analysis identified 447, 465 and 520 differentially expressed genes (DEGs) in the BME cells after LPS, S. aureus JE2 and S. aureus SA003 stimulation, respectively. A major differential response in the inflammatory gene expression was noticed between the stimulation of LPS and S. aureus strains. Unlike the S. aureus strains, LPS stimulation resulted in significant upregulation of CCL2, CXCL2, CXCL3, CXCL8, IL1α and IL1β, which were confirmed by qPCR analysis. Pam3CSK4 was not able to induce significant changes in the expression of cytokines and chemokines in challenged BME cells. The exogenous CyPA administration was able to upregulate CXCL2, CXCL3, CXCL8, IL1α and IL1β expression in BME cells indicating its ability to promote inflammation. The identification of transcriptional markers of mastitis specific for individual inflammatory factors such as LPS, Pam3CSK4 or CyPA, which can be evaluated in vitro in BME cells, may enable the development of novel diagnostics and/or immunomodulatory treatments, providing new tools for the effective management of mastitis in dairy cows. The results of this work are an advance in this regard.

scholarly journals LncRNA HCG11 inhibits adipocyte differentiation in human adipose-derived mesenchymal stem cells by sponging miR-204-5p to upregulate SIRT1

2020 ◽  
Author(s):  
Dandan Li ◽  
Yang Liu ◽  
Wei Gao ◽  
Jiakai Han ◽  
Rongrong Yuan ◽  
...  
Keyword(s):  
Target Genes ◽  
Adipocyte Differentiation ◽  
Inflammatory Responses ◽  
Inflammatory Factors ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Protein Levels ◽  
Suppressor Effect ◽  
Adipogenic Marker

Abstract Background: LncRNAs have been discovered to play a key role in adipogenesis, vital in regulating adipose developmen t. Numerous evidences show that adipogenesis is the leading cause of obesity, while the role of lncRNA HLA complex group 11 ( HCG11 ) in adipocyte differentiation has not been elucidated. Methods: hAdMSCs were used to establish a model of cell differentiation in vitro . Expression of lncRNA HCG11 was detected by RT-qPCR analysis. Transfection of the shRNA targeting HCG11 or pcDNA-HCG11 into hAdMSCs was also assessed. The adipogenic marker proteins C/EBPα, FABP4 and PPARγ2 and important inflammatory factors IL-6 and TNF-α were detected by Western blot. Bioinformatics analysis predicted the target genes of HCG11 and mir-204-5p, which was confirmed by luciferase reporter gene analysis and RNA pull-down analysis. Results: Here we show that lncRNA HCG11 was decreased as the degree of adipogenesis. The expression of C/EBPα, FABP4 and PPARγ2 were significantly downregulated transfected with pcDNA-HCG11 in hAdMSCs at different stages, while knockdown lncRNA HCG11 can promote adipocyte differentiation. In addition, miR-204-5p was a potential target gene of HCG11 and SIRT1 could directly target miR-204-5p. Overexpression of SIRT1 or transfected with agonists of SIRT1 (Res) significantly inhibited adipogenic marker protein levels and inflammatory responses, and the proliferation of hAdMSCs were also inhibited. pcDNA-HCG11 and miR-204-5p mimic were co-transfected into hAdMSCs, we found that miR-204-5p mimic reversed the suppressor effect of pcDNA-HCG11. Conclusion: Our findings showed that HCG11 negatively regulated cell proliferation, inflammatory responses and adipogenesis by miR-204-5p/SIRT1 axis. And our findings may provide a new target for the study of adipogenesis in hAdMSCs and obesity.

scholarly journals Lysosome-Dependent LXR and PPARδ Activation Upon Efferocytosis in Human Macrophages

2021 ◽  
Vol 12 ◽  
Author(s):  
Ana Carolina Mota ◽  
Monica Dominguez ◽  
Andreas Weigert ◽  
Ryan G. Snodgrass ◽  
Dmitry Namgaladze ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Target Genes ◽  
Inflammatory Responses ◽  
Regulatory Element ◽  
Peroxisome Proliferator ◽  
Liver X Receptors ◽  
Human Macrophages ◽  
Sterol Regulatory Element ◽  
Peroxisome Proliferator Activated Receptors ◽  
X Receptors

Efferocytosis is critical for tissue homeostasis, as its deregulation is associated with several autoimmune pathologies. While engulfing apoptotic cells, phagocytes activate transcription factors, such as peroxisome proliferator-activated receptors (PPAR) or liver X receptors (LXR) that orchestrate metabolic, phagocytic, and inflammatory responses towards the ingested material. Coordination of these transcription factors in efferocytotic human macrophages is not fully understood. In this study, we evaluated the transcriptional profile of macrophages following the uptake of apoptotic Jurkat T cells using RNA-seq analysis. Results indicated upregulation of PPAR and LXR pathways but downregulation of sterol regulatory element-binding proteins (SREBP) target genes. Pharmacological inhibition and RNA interference pointed to LXR and PPARδ as relevant transcriptional regulators, while PPARγ did not substantially contribute to gene regulation. Mechanistically, lysosomal digestion and lysosomal acid lipase (LIPA) were required for PPAR and LXR activation, while PPARδ activation also demanded an active lysosomal phospholipase A2 (PLA2G15). Pharmacological interference with LXR signaling attenuated ABCA1-dependent cholesterol efflux from efferocytotic macrophages, but suppression of inflammatory responses following efferocytosis occurred independently of LXR and PPARδ. These data provide mechanistic details on LXR and PPARδ activation in efferocytotic human macrophages.

scholarly journals Inflammatory Responses Induced by the Rupture of Intracranial Aneurysms Are Modulated by miRNAs

2019 ◽  
Vol 57 (2) ◽  
pp. 988-996 ◽  
Author(s):  
Michal Korostynski ◽  
Rafal Morga ◽  
Marcin Piechota ◽  
Dzesika Hoinkis ◽  
Slawomir Golda ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Blood Cells ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Chronic Phase ◽  
Mature Mirnas ◽  
Inflammatory Factors ◽  
Peripheral Blood Cells

Abstract Influence of an intracranial aneurysm (IA) rupture on the expression of miRNAs and the potential significance of the resulting changes remains poorly understood. We aimed to characterize the response to the IA rupture through the analysis of miRNAs in peripheral blood cells. Expression of small RNAs was investigated using deep transcriptome sequencing in patients in the acute phase of an IA rupture (first 72 h), in the chronic phase (3–15 months), and controls. A functional analysis and the potential interactions between miRNAs and target genes were investigated. We also measured the levels of proteins that were influenced by regulated miRNAs. We found that 106 mature miRNAs and 90 miRNA precursors were differentially expressed among the groups. The regulated miRNAs were involved in a variety of pathways, and the top pathway involved cytokine-cytokine receptor interactions. The identified miRNAs targeted the inflammatory factors HMGB1 and FASLG. Changes in their expression were detected at the mRNA and protein levels. IA rupture strongly influences the transcription profiles in peripheral blood cells. The regulated miRNAs were involved in the control of immune cell homeostasis. In summary, these results may aid in the elucidation of the molecular mechanisms that orchestrate the inflammatory response to IA rupture.

scholarly journals Analysis of the transcriptional logic governing differential spatial expression in Hh target genes

2018 ◽  
Author(s):  
Manuel Cambón ◽  
Óscar Sánchez
Keyword(s):  
Transcription Factors ◽  
Cellular Response ◽  
Target Genes ◽  
Threshold Model ◽  
Theoretical Models ◽  
Transcriptional Responses ◽  
Cubitus Interruptus ◽  
Spatial Expression ◽  
Complex Process ◽  
Transcription Process

AbstractThis work provides theoretical tools to analyse the transcriptional effects of certain biochemical mechanisms (i.e. affinity and cooperativity) that have been proposed in previous literature to explain the differential spatial expression of Hedgehog target genes involved in Drosophila development. Specifically we have focused on the expression of decapentaplegic and patched. The transcription of these genes is believed to be controlled by opposing gradients of the activator and repressor forms of the transcription factor Cubitus interruptus (Ci). This study is based on a thermodynamic approach, which provides expression rates for these genes. These expression rates are controlled by transcription factors which are competing and cooperating for common binding sites. We have made mathematical representations of the different expression rates which depend on multiple factors and variables. The expressions obtained with the model have been refined to produce simpler equivalent formulae which allow for their mathematical analysis. Thanks to this, we can evaluate the correlation between the different interactions involved in transcription and the biological features observed at tissular level. These mathematical models can be applied to other morphogenes to help understand the complex transcriptional logic of opposing activator and repressor gradients.Author summaryMorphogenic differentiation is a complex process that involves emission, reception and cellular response to different signals. It is well known that the same morphogenic signal can give rise to different cellular transcriptional responses that usually depend, among other factors, on transcription factors. In concordance with the activator threshold model, classically it has been distinguished between high and low threshold target genes in order to explain how cells receiving the same signal can activate different genes. However, in particular cases where the transcription is controlled by two opposing transcription factors, it has been tested that this logic is not valid. This motivates the necessity for describing new theoretical models in order to understand better these cellular responses. By a theoretical analysis we have deduced different versions of transcriptional logic that are significantly determined by how the opposing transcription factors cooperate between them in the transcription process. We have also tested these different scenarios focussing on the Drosophila Hh target genes, and we have reproduced similar conclusions to the ones obtained by other methodologies.

scholarly journals Inflammatory responses to secondary organic aerosols (SOA) generated from biogenic and anthropogenic precursors

2017 ◽  
Author(s):  
Wing Y. Tuet ◽  
Yunle Chen ◽  
Shierly Fok ◽  
Julie A. Champion ◽  
Nga L. Ng
Keyword(s):  
Cellular Response ◽  
Secondary Organic Aerosols ◽  
Inflammatory Responses ◽  
Organic Aerosols ◽  
Cellular Responses ◽  
Formation Condition ◽  
Ambient Aerosols ◽  
Health Implications ◽  
Cellular Effects ◽  
Tnf Α

Abstract. Cardiopulmonary health implications resulting from exposure to secondary organic aerosols (SOA), which comprise a significant fraction of ambient particulate matter (PM), have received increasing interest in recent years. In this study, alveolar macrophages were exposed to SOA generated from the photooxidation of biogenic and anthropogenic precursors (isoprene, α-pinene, β-caryophyllene, pentadecane, m-xylene, and naphthalene) under different formation conditions (RO2 + HO2 vs. RO2 + NO dominant, dry vs. humid). Various cellular responses were measured, including reactive oxygen/nitrogen species (ROS/RNS) production and secreted levels of cytokines, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). SOA precursor identity and formation condition affected all measured responses in a hydrocarbon-specific manner. With the exception of naphthalene SOA, cellular responses followed a trend where TNF-α levels reached a plateau with increasing IL-6 levels. ROS/RNS levels were consistent with relative levels of TNF-α and IL-6, due to their respective inflammatory and anti-inflammatory effects. Exposure to naphthalene SOA, whose aromatic ring-containing products may trigger different cellular pathways, induced higher levels of TNF-α and ROS/RNS than suggested by the trend. Distinct cellular response patterns were identified for hydrocarbons whose photooxidation products shared similar chemical functionalities and structures, which suggests that the carbon backbone may be important for determining cellular effects. A positive nonlinear correlation was also detected between ROS/RNS levels and previously measured DTT activities for SOA samples. In the context of ambient samples collected during summer and winter in the greater Atlanta area, all laboratory-generated SOA produced similar or higher levels of ROS/RNS and DTT activities. These results suggest that the health effects of SOA are important considerations for understanding the health implications of ambient aerosols.

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.

Sign in / Sign up

Export Citation Format

Share Document