Regulation Of Stress Response Research Articles

Heat stress transcription factors as the central molecular rheostat to optimize plant survival and recovery from heat stress.

Heat stress transcription factors (HSFs) are the core regulators of the heat stress (HS) response in plants. HSFs are considered as a molecular rheostat: their activities define the response intensity, incorporating information about the environmental temperature through a network of partner proteins. A prompted activation of HSFs is required for survival, for example the de novo synthesis of heat shock proteins. Furthermore, a timely attenuation of the stress response is necessary for the restoration of cellular functions and recovery from stress. In an ever-changing environment, the balance between thermotolerance and developmental processes such as reproductive fitness highlights the importance of a tightly tuned response. In many cases, the response is described as an ON/OFF mode, while in reality, it is very dynamic. This review compiles recent findings to update existing models about the HSF-regulated HS response and address two timely questions: How do plants adjust the intensity of cellular HS response corresponding to the temperature they experience? How does this adjustment contribute to the fine-tuning of the HS and developmental networks? Understanding these processes is crucial not only for enhancing our basic understanding of plant biology but also for developing strategies to improve crop resilience and productivity under stressful conditions.

Inflammatory gene regulation by Cdc42 in airway epithelial cells

Cytokine release from airway epithelial cells is a key immunological process that coordinates an immune response in the lungs. We propose that the Rho GTPase, Cdc42, regulates both transcription and trafficking of cytokines, ultimately affecting the essential process of cytokine release and subsequent inflammation in the lungs. Here, we examined the pro-inflammatory transcriptional profile that occurs in bronchial epithelial cells (BEAS-2B) in response to TNF-α using RNA-Seq and differential gene expression analysis. To interrogate the role of Cdc42 in inflammatory gene expression, we used a pharmacological inhibitor of Cdc42, ML141, and determined changes in the transcriptomic profile induced by Cdc42 inhibition. Our results indicated that Cdc42 inhibition with ML141 resulted in a unique inflammatory phenotype concomitant with increased gene expression of ER stress genes, Golgi membrane and vesicle transport genes. To further interrogate the inflammatory pathways regulated by Cdc42, we made BEAS-2B knockdown strains for the signaling targets TRIB3, DUSP5, SESN2 and BMP4, which showed high differential expression in response to Cdc42 inhibition. Depletion of DUSP5 and TRIB3 reduced the pro-inflammatory response triggered by Cdc42 inhibition as shown by a reduction in cytokine transcript levels. Depletion of SESN2 and BMP4 did not affect cytokine transcript level, however, Golgi fragmentation was reduced. These results provide further evidence that in airway epithelial cells, Cdc42 is part of a signaling network that controls inflammatory gene expression and secretion by regulating Golgi integrity.Summary sentence:We define the Cdc42-regulated gene networks for inflammatory signaling in airway epithelial cells which includes regulation of ER stress response and vesicle trafficking pathways.

Genome-Wide Identification and Characterization of Maize Long-Chain Acyl-CoA Synthetases and Their Expression Profiles in Different Tissues and in Response to Multiple Abiotic Stresses.

Long-chain acyl-CoA synthetases (LACSs) are essential enzymes that activate free fatty acids to fatty acyl-CoA thioesters, playing key roles in fatty acid (FA) catabolism, lipid synthesis and storage, epidermal wax synthesis, and stress tolerance. Despite their importance, comprehensive information about LACS genes in maize, a primary food crop, remains scarce. In the present work, eleven maize LACS genes were identified and mapped across five chromosomes. Three pairs of segmentally duplicated genes were detected in the maize LACS gene family, which underwent significant purifying selection (Ka/Ks < 1). Subsequently, phylogenetic analysis indicated that ZmLACS genes were divided into four subclasses, as supported by highly conserved motifs and gene structures. On the basis of the PlantCARE database, analysis of the ZmLACS promoter regions revealed various cis-regulatory elements related to tissue-specific expression, hormonal regulation, and abiotic stress response. RT-qPCR analysis showed that ZmLACS genes exhibit tissue-specific expression patterns and respond to diverse abiotic stresses including drought and salt, as well as phytohormone abscisic acid. Furthermore, using the STRING database, several proteins involved in fatty acid and complex lipid synthesis were identified to be the potential interaction partners of ZmLACS proteins, which was also confirmed by the yeast two-hybrid (Y2H) assay, enhancing our understanding of wax biosynthesis and regulatory mechanisms in response to abiotic stresses in maize. These findings provide a comprehensive understanding of ZmLACS genes and offer a theoretical foundation for future research on the biological functions of LACS genes in maize environmental adaptability.

Transcription factor TaNF-YB2 interacts with partners TaNF-YA7/YC7 and transcriptionally activates distinct stress-defensive genes to modulate drought tolerance in T. Aestivum

BackgroundDrought stress limits significantly the crop productivity. However, plants have evolved various strategies to cope with the drought conditions by adopting complex molecular, biochemical, and physiological mechanisms. Members of the nuclear factor Y (NF-Y) transcription factor (TF) family constitute one of the largest TF classes and are involved in plant responses to abiotic stresses.ResultsTaNF-YB2, a NY-YB subfamily gene in T. aestivum, was characterized in this study focusing on its role in mediating plant adaptation to drought stress. Yeast two-hybrid (Y-2 H), biomolecular fluoresence complementation (BiFC), and Co-immunoprecipitation (Co-IP) assays indicated that TaNF-YB2 interacts with the NF-YA member TaNF-YA7 and NF-YC family member TaNF-YC7, which constitutes a heterotrimer TaNF-YB2/TaNF-YA7/TaNF-YC7. The TaNF-YB2 transcripts are induced in roots and aerial tissues upon drought signaling; GUS histochemical staining analysis demonstrated the roles of cis-regulatory elements ABRE and MYB situated in TaNF-YB2 promoter to contribute to target gene response to drought. Transgene analysis on TaNF-YB2 confirmed its functions in regulating drought adaptation via modulating stomata movement, osmolyte biosynthesis, and reactive oxygen species (ROS) homeostasis. TaNF-YB2 possessed the abilities in transcriptionally activating TaP5CS2, the P5CS family gene involving proline biosynthesis and TaSOD1, TaCAT5, and TaPOD5, the genes encoding antioxidant enzymes. Positive correlations were found between yield and the TaNF-YB2 transcripts in a core panel constituting 45 wheat cultivars under drought condition, in which two types of major haplotypes including TaNF-YB2-Hap1 and -Hap2 were included, with the former conferring more TaNF-YB2 transcripts and stronger plant drought tolerance.ConclusionsTaNF-YB2 is transcriptional response to drought stress. It is an essential regulator in mediating plant drought adaptation by modulating the physiological processes associated with stomatal movement, osmolyte biosynthesis, and reactive oxygen species (ROS) homeostasis, depending on its role in transcriptionally regulating stress response genes. Our research deepens the understanding of plant drought stress underlying NF-Y TF family and provides gene resource in efforts for molecular breeding the drought-tolerant cultivars in T. aestivum.

Overexpression of FERONIA receptor kinase MdMRLK2 regulates lignin accumulation and enhances water use efficiency in apple under long-term water deficit condition.

Water use efficiency (WUE) is crucial for apple tree fitness and survival, especially in response to climatic changes. The receptor-like kinase FERONIA is reportedly an essential regulator of plant stress responses, but its role in regulating WUE under water deficit conditions is unclear. Here, we found that overexpressing the apple FERONIA receptor kinase gene, MdMRLK2, enhanced apple WUE under long-term water deficit conditions. Under drought treatment, 35S::MdMRLK2 apple plants exhibited higher photosynthetic capacity and antioxidant enzyme activities than wild-type (WT) plants. 35S::MdMRLK2 apple plants also showed increased biomass accumulation, root activity, and water potential compared to WT plants. Moreover, MdMRLK2 physically interacts with and phosphorylates cinnamoyl-CoA reductase 1, MdCCR1, an enzyme essential for lignin synthesis, at position Ser260. This interaction likely contributed to increased vessel density, vascular cylinder area, and lignin content in 35S::MdMRLK2 apple plants under drought conditions. Therefore, our findings reveal a novel function of MdMRLK2 in regulating apple WUE under water deficit conditions.

Characterization and stress-responsive regulation of CmPHT1 genes involved in phosphate uptake and transport in Melon (Cucumis melo L.)

BackgroundPhosphorus (P) deficiency, a major nutrient stress, greatly hinders plant growth. Phosphate (Pi) uptake in plant roots relies on PHT1 family transporters. However, melon (Cucumis melo L.) lacks comprehensive identification and characterization of PHT1 genes, particularly their response patterns under diverse stresses.ResultsThis study identified and analyzed seven putative CmPHT1 genes on chromosomes 3, 4, 5, 6, and 7 using the melon genome. Phylogenetic analysis revealed shared motifs, domain compositions, and evolutionary relationships among genes with close histories. Exon number varied from 1 to 3. Collinearity analysis suggested segmental and tandem duplications as the primary mechanisms for CmPHT1 gene family expansion. CmPHT1;4 and CmPHT1;5 emerged as a tandemly duplicated pair. Analysis of cis-elements in CmPHT1 promoters identified 14 functional categories, including putative PHR1-binding sites (P1BS) in CmPHT1;4, CmPHT1;6, and CmPHT1;7. We identified that three WRKY transcription factors regulated CmPHT1;5 expression by binding to its W-box element. Notably, CmPHT1 promoters harbored cis-elements responsive to hormones and abiotic factors. Different stresses regulated CmPHT1 expression differently, suggesting that the adjusted expression patterns might contribute to plant adaptation.ConclusionsThis study unveils the characteristics, evolutionary diversity, and stress responsiveness of CmPHT1 genes in melon. These findings lay the foundation for in-depth investigations into their functional mechanisms in Cucurbitaceae crops.

Ghrelin, Neuroinflammation, Oxidative Stress, and Mood Disorders: What Are the Connections?

Ghrelin is a gut peptide hormone associated with feeding behavior and energy homeostasis. Acylated ghrelin binds to the growth hormone secretagogue receptor 1a subtype (GHS-R1a) in the hippocampus, leading to GH release from the anterior pituitary. However, in recent years, ghrelin and its receptor have also been implicated in other processes, including the regulation of cardiomyocyte function, muscle trophism, and bone metabolism. Moreover, GHS-R1a is distributed throughout the brain and is expressed in brain areas that regulate the stress response and emotional behavior. Consistently, a growing body of evidence supports the role of ghrelin in regulating stress response and mood. Stress has consistently been shown to increase ghrelin levels, and despite some inconsistencies, both human and rodent studies suggested antidepressant effects of ghrelin. Nevertheless, the precise mechanism by which ghrelin influences stress response and mood remains largely unknown. Intriguingly, ghrelin and GHS-R1a were consistently reported to exert anti-inflammatory, antioxidant, and neurotrophic effects both in vivo and in vitro, although this has never been directly assessed in relation to psychopathology. In the present review we will discuss available literature linking ghrelin with the stress response and depressive-like behavior in animal models as well as evidence describing the interplay between ghrelin and neuroinflammation/oxidative stress. Although further studies are required to understand the mechanisms involved in the action of ghrelin on mood, we hypothesize that the antiinflammatory and anti-oxidative properties of ghrelin may give a key contribution.

Early stress in maternal deprivation affects the expression of OX1R in the limbic system of the brain and contributes to the development of anxiety-depressive symptoms in rats

BACKGROUND: Depressive states are becoming an increasingly common mental disorder and a serious social problem that places a heavy economic burden on society. Increasing data from preclinical and clinical studies indicate that orexins (neuropeptides, also known as hypocretins) and their receptors are involved in the pathogenesis of depression. The orexinergic system regulates disrupted functions in depressive states, such as sleep, reward system, eating behavior, stress response, and monoaminergic regulation. However, the exact role of orexins in behavioral and neurophysiological disorders in depression is still unclear. AIM: This study aimed to examine the effect of early postnatal stress on the expression of OX1R orexin in the limbic system and the development of anxiety-depressive symptoms in rats. MATERIALS AND METHODS: Maternal deprivation was used as a model of early postnatal stress (postpartum days 2–12). The animals were divided into the control (n = 20) and maternal deprivation (n = 20) groups. On day 90 of life, the influence of early postnatal stress on the development of anxiety-depressive symptoms in adult rats was analyzed using a package of behavioral tests, namely, raised cruciform maze, forced swimming Porsolt test, and two-bottle test. After the experiments, the animals were killed by decapitation, the brain was extracted and placed in the cold, and brain structures (hypothalamus and amygdala) were isolated, immediately frozen in liquid nitrogen, and stored at a temperature of −80°C for polymerase chain reaction analysis. RESULTS: In the “raised cruciform maze,” the maternal deprivation group spent less time in the open arms of the maze, and the time spent in the closed sleeves increased relative to the control, which can be assessed as an increase in anxiety levels. In the Porsolt test, the maternal deprivation group had increased immobilization time relative to the control group. In the two-bottle sucrose preference test, the maternal deprivation group demonstrated a decreased preference for sucrose solution, which indicates the development of anhedonia. In the hypothalamus, the mRNA expression level of OX1R significantly decreased in the experimental group compared with that in the control group. A twofold decrease in the mRNA expression level of OX1R was also observed in the amygdala of the experimental group compared with that of the control group. CONCLUSIONS: Early stress caused by maternal deprivation resulted in a decrease in OX1R orexin expression in the hypothalamus and amygdala and contributed to the development of anxiety-depressive symptoms in rats.

Germline regulation of the somatic mitochondrial stress response

Mitochondria are pivotal organelles for cellular energy production and the regulation of stress responses. Recent research has elucidated complex mechanisms through which mitochondrial stress in one tissue can impact distant tissues, thereby promoting overall organismal health. Two recent studies by Shen et al. and Charmpilas et al. have demonstrated that an intact germline serves as a crucial signaling hub for the activation of the somatic mitochondrial unfolded protein response (UPRmt) in Caenorhabditis elegans.

Role of M6a Methylation in Myocardial Ischemia-Reperfusion Injury and Doxorubicin-Induced Cardiotoxicity.

Cardiovascular disease remains the leading cause of death worldwide, with acute myocardial infarction and anticancer drug-induced cardiotoxicity being the significant factors. The most effective treatment for acute myocardial infarction is rapid restoration of coronary blood flow by thrombolytic therapy or percutaneous coronary intervention. However, myocardial ischemia-reperfusion injury (MI/RI) after reperfusion therapy is common in acute myocardial infarction, thus affecting the prognosis of patients with acute myocardial infarction. There is no effective treatment for MI/RI. Anthracyclines such as Doxorubicin (DOX) have limited clinical use due to their cardiotoxicity, and the mechanism of DOX-induced cardiac injury is complex and not yet fully understood. N6-methyladenosine (m6A) plays a crucial role in many biological processes. Emerging evidence suggests that m6A methylation plays a critical regulatory role in MI/RI and DOX-induced cardiotoxicity (DIC), suggesting that m6A may serve as a novel biomarker and therapeutic target for MI/RI and DIC. M6A methylation may mediate the pathophysiological processes of MI/RI and DIC by regulating cellular autophagy, apoptosis, oxidative stress, and inflammatory response. In this paper, we first focus on the relationship between m6A methylation and MI/RI, then further elucidate that m6A methylation may mediate the pathophysiological process of MI/RI through the regulation of cellular autophagy, apoptosis, oxidative stress, and inflammatory response. Finally, briefly outline the roles played by m6A in DIC, which will provide a new methodology and direction for the research and treatment of MI/RI and DIC.

Homologous Delta-12 Fatty Acid Desaturase (FAD2) Genes Affect Gene Expression and Linoleic Acid Levels in Lentinula edodes under Heat Stress.

Delta-12 fatty acid desaturases (FAD2s) actively regulate stress responses and cell differentiation in living organisms. In this study, six homologous FAD2 genes were identified based on the genome sequence of Lentinula edodes. Then, the six FAD2 protein sequences were analyzed using bioinformatics tools, including ExPASy ProtParam, SignalP, TMHMM, and TargetP. These analyses were performed to predict the physical and chemical properties, signal peptides, and transmembrane and conserved domains of these proteins. The polypeptide sequences were aligned, and a maximum likelihood phylogenetic tree was constructed using MEGA 7.0 software to elucidate the phylogenetic relationships between homologous FAD2 sequences. The results demonstrated that the FAD2 proteins contained three conserved histidine-rich regions (HXXXH, HXXHH, and HXXHH), which included eight histidine residues. The linoleic acid content and FAD2 enzyme activity were further analyzed, and the levels in the mutagenic heat-tolerant strain 18N44 were lower than those in the wild-type strain 18. Interestingly, the expression levels of the FAD2-2 and FAD2-3 genes under heat stress in strain 18N44 were lower than those in strain 18. These findings indicated that FAD2-2 and FAD2-3 may play major roles in the synthesis of linoleic acid during heat stress.

Protein Kinase A Negatively Regulates the Acetic Acid Stress Response in S. cerevisiae.

Bioethanol fermentation from lignocellulosic hydrolysates is negatively affected by the presence of acetic acid. The budding yeast S. cerevisiae adapts to acetic acid stress partly by activating the transcription factor, Haa1. Haa1 induces the expression of many genes, which are responsible for increased fitness in the presence of acetic acid. Here, we show that protein kinase A (PKA) is a negative regulator of Haa1-dependent gene expression under both basal and acetic acid stress conditions. Deletions of RAS2, encoding a positive regulator of PKA, and PDE2, encoding a negative regulator of PKA, lead to an increased and decreased expression of Haa1-regulated genes, respectively. Importantly, the deletion of HAA1 largely reverses the effects of ras2∆. Additionally, the expression of a dominant, hyperactive RAS2A18V19 mutant allele also reduces the expression of Haa1-regulated genes. We found that both pde2Δ and RAS2A18V19 reduce cell fitness in response to acetic acid stress, while ras2Δ increases cellular adaptation. There are three PKA catalytic subunits in yeast, encoded by TPK1, TPK2, and TPK3. We show that single mutations in TPK1 and TPK3 lead to the increased expression of Haa1-regulated genes, while tpk2Δ reduces their expression. Among tpk double mutations, tpk1Δ tpk3Δ greatly increases the expression of Haa1-regulated genes. We found that acetic acid stress in a tpk1Δ tpk3Δ double mutant induces a flocculation phenotype, which is reversed by haa1Δ. Our findings reveal PKA to be a negative regulator of the acetic acid stress response and may help engineer yeast strains with increased efficiency of bioethanol fermentation.

Altered hypoxia-induced cellular responses and inflammatory profile in lung fibroblasts from COPD patients compared to control subjects

BackgroundChronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by chronic bronchitis, emphysema and vascular remodelling. The disease is associated with hypoxia, inflammation and oxidative stress. Lung fibroblasts are important cells in remodelling processes in COPD, as main producers of extracellular matrix proteins but also in synthesis of growth factors and inflammatory mediators.MethodsIn this study we aimed to investigate if there are differences in how primary distal lung fibroblasts obtained from COPD patients and healthy subjects respond to hypoxia (1% O2) and pro-fibrotic stimuli with TGF-β1 (10 ng/mL). Genes and proteins associated with oxidative stress, endoplasmic reticulum stress, remodelling and inflammation were analysed with RT-qPCR and ELISA.ResultsHypoxia induced differences in expression of genes involved in oxidative stress (SOD3 and HIF-1α), ER stress (IRE1, PARK and ATF6), apoptosis (c-Jun and Bcl2) and remodelling (5HTR2B, Collagen7 and VEGFR2) in lung fibroblasts from COPD subjects compared to control subjects, where COPD fibroblasts were in general less responsive. The release of VEGF-C was increased after hypoxia, whereas TGF-β significantly reduced the VEGF response to hypoxia and the release of HGF. COPD fibroblasts had a higher release of IL-6, IL-8, MCP-1 and PGE2 compared to lung fibroblasts from control subjects. The release of inflammatory mediators was less affected by hypoxia, whereas TGFβ1 induced differences in inflammatory profile between fibroblasts from COPD and control subjects.ConclusionThese results suggest that there is an alteration of gene regulation of various stress responses and remodelling associated mediator release that is related to COPD and hypoxia, where fibroblasts from COPD patients have a deficient response.

Plant responses to abiotic stress regulated by histone acetylation.

In eukaryotes, histone acetylation and deacetylation play an important role in the regulation of gene expression. Histone acetylation levels are reversibly regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs). Increasing evidence highlights histone acetylation plays essential roles in the regulation of gene expression in plant response to environmental stress. In this review, we discussed the recent advance of histone acetylation in the regulation of abiotic stress responses including temperature, light, salt and drought stress. This information will contribute to our understanding of how plants adapt to environmental changes. As the mechanisms of epigenetic regulation are conserved in many plants, research in this field has potential applications in improvement of agricultural productivity.

Influence of Diet on Reproducible Corticosterone Levels in a Mouse Model of Maternal Separation with Early Weaning.

Maternal separation with early weaning (MSEW) is a popular early life stress (ELS) model in rodents, which emulates childhood neglect through scheduled mother-offspring separation. Although variations of ELS models, including maternal separation and MSEW, have been published for the mouse species, the reported results are inconsistent. Corticosterone is considered the main stress hormone involved in regulating stress responses in rodents-yet generating a robust and reproducible corticosterone response in mouse models of ELS has been elusive. Considering the current lack of standardization for MSEW protocols, these inconsistent results may be attributed to variations in model methodologies. Here, we compared the effects of select early wean diet sources-which are the non-milk diets used to complete early weaning in MSEW pups-on the immediate stress phenotype of C57BL/6J mice at postnatal day 21. Non-aversive handling was an integral component of our modified MSEW model. The evaluation of body weight and serum corticosterone revealed the early wean diet to be a key variable in the resulting stress phenotype. Interestingly, select non-milk diets facilitated a stress phenotype in which low body weight was accompanied by significant corticosterone elevation. Our data indicate that dietary considerations are critical in MSEW-based studies and provide insight into improving the reproducibility of key stress-associated outcomes as a function of this widely used ELS paradigm.

Regulation of oxidative stress response and antioxidant modification in Corynebacterium glutamicum.

As an efficient and safe industrial bacterium, Corynebacterium glutamicum has extensive application in amino acid production. However, it often faces oxidative stress induced by reactive oxygen species (ROS), leading to diminished production efficiency. To enhance the robustness of C. glutamicum, numerous studies have focused on elucidating its regulatory mechanisms under various stress conditions such as heat, acid, and sulfur stress. However, a comprehensive review of its defense mechanisms against oxidative stress is needed. This review offers an in-depth overview of the mechanisms C. glutamicum employs to manage oxidative stress. It covers both enzymatic and non-enzymatic systems, including antioxidant enzymes, regulatory protein families, sigma factors involved in transcription, and physiological redox reduction pathways. This review provides insights for advancing research on the antioxidant mechanisms of C. glutamicum and sheds light on its potential applications in industrial production.

Regulation of Common Early and Late Stress Responses in Rice by Transcriptional and Antioxidant Mechanisms Under Salt Stress

Regulation of Common Early and Late Stress Responses in Rice by Transcriptional and Antioxidant Mechanisms Under Salt Stress

UBAP2L contributes to formation of P-bodies and modulates their association with stress granules.

Stress triggers the formation of two distinct cytoplasmic biomolecular condensates: stress granules (SGs) and processing bodies (PBs), both of which may contribute to stress-responsive translation regulation. Though PBs can be present constitutively, stress can increase their number and size and lead to their interaction with stress-induced SGs. The mechanism of such interaction, however, is largely unknown. Formation of canonical SGs requires the RNA binding protein Ubiquitin-Associated Protein 2-Like (UBAP2L), which is a central SG node protein in the RNA-protein interaction network of SGs and PBs. UBAP2L binds to the essential SG and PB proteins G3BP and DDX6, respectively. Research on UBAP2L has mostly focused on its role in SGs, but not its connection to PBs. We find that UBAP2L is not solely an SG protein but also localizes to PBs in certain conditions, contributes to PB biogenesis and SG-PB interactions, and can nucleate hybrid granules containing SG and PB components in cells. These findings inform a new model for SG and PB formation in the context of UBAP2L's role.

Autotaxin Inhibition Reduces Post-Ischemic Myocardial Inflammation via Epigenetic Gene Modifications.

Myocardial infarction (MI) triggers a complex inflammatory response that is essential for cardiac repair but can also lead to adverse outcomes if left uncontrolled. Recent studies have highlighted the importance of epigenetic modifications in regulating post-MI inflammation. This study investigated the role of the autotaxin (ATX)/lysophosphatidic acid (LPA) signaling axis in modulating myocardial inflammation through epigenetic pathways in a mouse model of MI. C57BL/6J mice underwent left anterior descending coronary artery ligation to induce MI and were treated with the ATX inhibitor, PF-8380, or vehicle. Cardiac tissue from the border zone was collected at 6h, 1, 3, and 7days post-MI for epigenetic gene profiling using RT2 Profiler PCR Arrays. The results revealed distinct gene expression patterns across sham, MI + Vehicle, and MI + PF-8380 groups. PF-8380 treatment significantly altered the expression of genes involved in inflammation, stress response, and epigenetic regulation compared to the vehicle group. Notably, PF-8380 downregulated Hdac5, Prmt5, and Prmt6, which are linked to exacerbated inflammatory responses, as early as 6h post-MI. Furthermore, PF-8380 attenuated the reduction of Smyd1, a gene important in myogenic differentiation, at 7days post-MI. This study demonstrates that the ATX/LPA signaling axis plays a pivotal role in modulating post-MI inflammation via epigenetic pathways. Targeting ATX/LPA signaling may represent a novel therapeutic strategy to control inflammation and improve outcomes after MI. Further research is needed to validate these findings in preclinical and clinical settings and to elucidate the complex interplay between epigenetic mechanisms and ATX/LPA signaling in the context of MI.

Transcriptional and post-transcriptional mechanisms modulate cyclopropane fatty acid synthase through small RNAs in Escherichia coli.

Bacteria experience many environmental stresses that challenge their membrane integrity. To withstand these challenges, bacteria sense what stress is occurring and mount a response that protects membranes. Previous work documented the important roles of small RNA (sRNA) regulators in membrane stress responses. One sRNA, RydC, helps cells cope with membrane-disrupting stresses by promoting changes in the types of lipids incorporated into membranes. In this study, we identified a regulator, YieP, that controls when RydC is produced and additional sRNA regulators that modulate YieP levels and RydC activity. These findings illuminate a complex regulatory network that helps bacteria sense and respond to membrane stress.