Thirty years ago, there was an emerging appreciation for the significance of oxidative stress in newborn disease. This prompted a renewed interest in the impact of oxygen therapy for the newborn in ...the delivery room and beyond, especially in premature infants. Today, the complexity of oxidative stress both in normal regulation and pathology is better understood, especially as it relates to neonatal mitochondrial oxidative stress responses to hyperoxia. Mitochondria are recipients of oxidative damage and have a propensity for oxidative self-injury that has been implicated in the pathogenesis of neonatal lung diseases. Similarly, both intrauterine growth restriction (IUGR) and macrosomia are associated with mitochondrial dysfunction and oxidative stress. Additionally, reoxygenation with 100% O2 in a hypoxic-ischemic newborn lamb model increased the production of pro-inflammatory cytokines in the brain. Moreover, the interplay between inflammation and oxidative stress in the newborn is better understood because of animal studies. Transcriptomic analyses have found a number of genes to be differentially expressed in murine models of bronchopulmonary dysplasia (BPD). Epigenetic changes have also been detected both in animal models of BPD and premature infants exposed to oxygen. Antioxidant therapy to prevent newborn disease has not been very successful; however, new therapeutic principles, like melatonin, are under investigation.
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•Oxidative stress contributes to many neonatal disease states.•Mitochondria are important sources of reactive oxygen species in neonates.•Growth abnormalities and inflammation contribute to oxidative stress in neonates.•Oxidative stress induces changes in gene regulation and epigenetics.•Antioxidants have not been proven to decrease disease burden in neonates.
Abiotic stress causes alterations in physiological, biochemical and metabolic equilibrium in the plant cells, leading to reduction in protein turn-over, change in post translational modification of ...proteins, impaired photosynthetic capability and increase in ROS production. The stress-induced ROS at higher levels can trigger oxidation of biomolecules, decomposition of membranes, inactivation of enzymes and alteration in gene expression. On the other hand, ROS is also detected by its sensors and signal transduction pathways are activated, which further transports the signal to the nucleus through redox reactions and involvement of Mitogen-activated Protein Kinase (MAPK) pathway. Consequently, change in gene expression patterns is instigated by involvement of stress-regulated cis-acting elements (ARE, CORE, W-box, GCC box, as-1 like) and stress-responsive transcription factors (NAC, MYB, WRKY, RAV, bZIP, AP2/ERF, ZAT). Finally, these gene products are transmitted back to the cell organelles to facilitate prevention from oxidative damage. Additionally, epigenetic changes play a central role in mediating cellular responses to abiotic stresses. Here, we review the recent updates on ROS-mediated signaling and monitoring of transcriptional and epigenetic changes that occur in a cell due to oxidative stress.
•During abiotic stress, a misbalance between generation and scavenging of ROS occurs and cellular homeostasis may be lost.•Thus, ROS-mediated signaling pathway and secondary messengers are activated to maintain appropriate concentration.•ROS-generated signals are transported to the nucleus, which instigates transcriptional and epigenetic reprogramming.
Abstract
To better adapt transiently or lastingly to stimuli from the surrounding environment, the chromatin states in plant cells vary to allow the cells to fine-tune their transcriptional profiles. ...Modifications of chromatin states involve a wide range of post-transcriptional histone modifications, histone variants, DNA methylation, and activity of non-coding RNAs, which can epigenetically determine specific transcriptional outputs. Recent advances in the area of ‘-omics’ of major crops have facilitated identification of epigenetic marks and their effect on plant response to environmental stresses. As most epigenetic mechanisms are known from studies in model plants, we summarize in this review recent epigenetic studies that may be important for improvement of crop adaptation and resilience to environmental changes, ultimately leading to the generation of stable climate-smart crops. This has paved the way for exploitation of epigenetic variation in crop breeding.
Intense breeding has narrowed crop genetic diversity. Epigenetic diversity could emerge as new source of phenotypic variations to improve crop adaptation to a changing environment and generate stable climate-smart crops.
The number of patients with chronic kidney disease (CKD) is on the rise worldwide, and there is urgent need for the development of effective plans against the increasing incidence of CKD. Podocytes, ...glomerular epithelial cells, are an integral part of the primary filtration unit of the kidney and form a slit membrane as a barrier to prevent proteinuria. The role of podocytes in the pathogenesis and progression of CKD is now recognized. Podocyte function depends on a specialized morphology with the arranged foot processes, which is directly related to their function. Epigenetic changes responsible for the regulation of gene expression related to podocyte morphology have been shown to be important in the pathogenesis of CKD. Although epigenetic mechanisms include DNA methylation, histone modifications, and RNA-based regulation, we have focused on DNA methylation changes because they are more stable than other epigenetic modifications. This review summarizes recent literature about the role of altered DNA methylation in the kidney, especially in glomerular podocytes, focusing on transcription factors and DNA damage responses that are closely associated with the formation of DNA methylation changes.
Introduction
Diabetes mellitus is a condition in which either the pancreas does not produce enough insulin, or the cells of the body do not respond properly to the insulin produced, resulting in high ...levels of sugar in the bloodstream. We hypothesized that epigenetic changes in pancreatic beta cells in the pancreas, the main insulin‐producing cells in the body, may contribute to the etiology of diabetes.
Methods
To test this hypothesis, we treated human pancreatic beta cells derived from induced pluripotent stem cells (iPSCs) with either high (20 mM) or low (2 mM) glucose for 14 days.
Results
We found epigenetic changes in several hundred genes, including those involved in many signaling pathways, especially glucose metabolism and insulin secretion. Other pathways affected were those involved in oxytocin metabolism, gastric acid secretion, calcium signaling, and adrenergic signaling.
Conclusion
Our study suggests that diabetes may, at least in part, be caused by epigenetic changes in pancreatic beta cells.
This is from the Experimental Biology 2019 Meeting. There is no full text article associated with this published in The FASEB Journal.
Colorectal cancer (CRC), a leading cause of cancer-related mortalities globally, results from the accumulation of multiple genetic and epigenetic alterations in the normal colonic and rectum ...epithelium, leading to the progression from colorectal adenomas to invasive carcinomas. Almost half of CRC patients will develop metastases in the course of the disease and most patients with metastatic CRC are incurable. Particularly, the 5-year survival rate of patients with stage 4 CRC at diagnosis is less than 10%. Although genetic understanding of these CRC tumors and paired metastases has led to major advances in elucidating early driver genes responsible for carcinogenesis and metastasis, the pathophysiological contribution of transcriptional and epigenetic aberrations in this malignancy which influence many central signaling pathways have attracted attention recently. Therefore, treatments that could affect several different molecular pathways may have pivotal implications for their efficacy. In this review, we summarize our current knowledge on the molecular network of CRC, including cellular signaling pathways, CRC microenvironment modulation, epigenetic changes, and CRC biomarkers for diagnosis and predictive/prognostic use. We also provide an overview of opportunities for the treatment and prevention strategies in this field.
Stem cells play central roles in tissue development, homeostasis, and regeneration. Decades of scientific research have uncovered processes of stem cell decline in tissue and organismal aging, and ...more recently, pioneering technologies permit the dissection of its underlying mechanisms and inform therapeutic development for aging and aging-associated disorders. In this review, we elucidate aging-related features across different somatic stem cell types, with a specific focus on epigenetic changes, loss of protein homeostasis, and systemic influencing factors, including chronic inflammation, circadian rhythm dysregulation, and metabolic disorder. Our survey of organismal stem cell aging summarizes its underlying biological implications, points to potential biomarkers of stem cell aging, and discusses stem cell-based therapeutic strategies with the potential for promoting healthy aging and combating aging and age-related diseases.
Liu et al. review the landscape of stem cell aging to elucidate aging-related features and mechanisms and interventions for different somatic stem cell types, with a particular focus on epigenetic changes, loss of protein homeostasis, and systemic influencing mechanisms such as chronic inflammation, circadian regulation, and metabolic disturbances.
DNA methylation at CpG dinucleotides is an important epigenetic regulator common to virtually all mammalian cell types, but recent evidence indicates that during early postnatal development neuronal ...genomes also accumulate uniquely high levels of two alternative forms of methylation, non-CpG methylation and hydroxymethylation. Here we discuss the distinct landscape of DNA methylation in neurons, how it is established, and how it might affect the binding and function of protein readers of DNA methylation. We review studies of one critical reader of DNA methylation in the brain, the Rett syndrome protein methyl CpG-binding protein 2 (MeCP2), and discuss how differential binding affinity of MeCP2 for non-CpG and hydroxymethylation may affect the function of this methyl-binding protein in the nervous system.
A defective epithelial barrier is found in patients with allergic rhinitis (AR) and asthma; however, the underlying mechanisms remain poorly understood. Histone deacetylase (HDAC) activity has been ...identified as a crucial driver of allergic inflammation and tight junction dysfunction.
We investigated whether HDAC activity has been altered in patients with AR and in a mouse model of house dust mite (HDM)–induced allergic asthma and whether it contributed to epithelial barrier dysfunction.
Primary nasal epithelial cells of control subjects and patients with AR were cultured at the air-liquid interface to study transepithelial electrical resistance and paracellular flux of fluorescein isothiocyanate–dextran (4 kDa) together with mRNA expression and immunofluorescence staining of tight junctions. Air-liquid interface cultures were stimulated with different concentrations of JNJ-26481585, a broad-spectrum HDAC inhibitor. In vivo the effect of JNJ-26481585 on mucosal permeability and tight junction function was evaluated in a mouse model of HDM-induced allergic airway inflammation.
General HDAC activity was greater in nasal epithelial cells of patients with AR and correlated inversely with epithelial integrity. Treatment of nasal epithelial cells with JNJ-26481585 restored epithelial integrity by promoting tight junction expression and protein reorganization. HDM-sensitized mice were treated with JNJ-26481585 to demonstrate the in vivo role of HDACs. Treated mice did not have allergic airway inflammation and had no bronchial hyperreactivity. Moreover, JNJ-26481585 treatment restored nasal mucosal function by promoting tight junction expression.
Our findings identify increased HDAC activity as a potential tissue-injury mechanism responsible for dysregulated epithelial cell repair, leading to defective epithelial barriers in AR. Blocking HDAC activity is a promising novel target for therapeutic intervention in patients with airway diseases.
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Abstract Helicobacter pylori ( H. pylori ) infect over half of the world’s population. The prevalence of H. pylori infection and the predominant genotype of H. pylori virulence factors vary ...considerably across different geographical regions. H. pylori could uniquely persist for decades in the harsh stomach environment, where it damages the gastric mucosa and changes the pattern of gastric hormone release, thereby affects gastric physiology. By utilizing various virulence factors, H. pylori targets different cellular proteins to modulate the host inflammatory response and initiate multiple “hits” on the gastric mucosa, resulting in chronic gastritis and peptic ulceration. Among the long-term consequences of H. pylori infection is gastric malignancies, particularly gastric cancer (GC) and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. As such, H. pylori has been recognized as a class I carcinogen by the International Agency for Research on Cancer. Despite a close causal link between H. pylori infection and the development of gastric malignancies, the precise mechanisms involved in this process are still obscure. Studies over the past two decades have revealed that H. pylori exert oncogenic effects on gastric mucosa through a complex interaction between bacterial factors, host factors, and environmental factors. Numerous signaling pathways can be activated by H. pylori. In this review, we aim to elaborate on the recent developments in the pathophysiological mechanisms of H. pylori -induced gastric inflammation and gastric cancer.
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