Nickel-induced transcriptional memory in lung epithelial cells promotes interferon signaling upon nicotine exposure
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ABSTRACT:
PROVIDER: PRJNA1014742 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25993500.fastq.gz | Fastqsanger.gz | |||
| SRR25993501.fastq.gz | Fastqsanger.gz | |||
| SRR25993502.fastq.gz | Fastqsanger.gz | |||
| SRR25993503.fastq.gz | Fastqsanger.gz | |||
| SRR25993504.fastq.gz | Fastqsanger.gz |
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Project description:Nickel is an environmental toxicant prevalent in the atmosphere. Nickel exposure is associated with a multitude of human health hazards including chronic respiratory ailments and lung and nasal cancers. Our earlier studies on nickel exposure in lung cells showed that a majority of the gene expression changes caused by nickel exposure persisted even after termination of exposure (nickel-washed-out cells (NiW)). In this study, we wanted to examine the impact of a secondary toxicant exposure on the nickel-washed-out (NiW) cells as compared to the cells that were never exposed to nickel. To accomplish this, we exposed the untreated control cells (UT) and the nickel-washed-out cells (NiW) to multiple doses of nicotine (NTE). RNA-Seq analysis showed that the exposure of NiW cells to nicotine (NiW-NTE) caused unique gene expression changes that were markedly different from the gene expression changes caused by nicotine exposure of UT cells, which were never exposed to nickel. Analysis of the differentially expressed genes using Reactome Pathway analysis predicted interferon signaling only in the NiW-NTE cells. Upstream Regulator Analysis (URA) predicted STAT-1, a transcription factor that mediates cellular response to interferons, as the top potential upstream regulator in the NiW-NTE cells. Furthermore, chromatin immunoprecipitation (ChIP) analysis revealed increased STAT-1 binding at the promoters of genes associated with interferon signaling in NiW-NTE cells. Aberrant STAT-1 activation has been shown to promote carcinogenesis and interferon signaling promotes pathogenesis of autoimmune disease. Therefore, our results suggest that the epigenetic and transcriptional memory of the cells from the previous nickel exposure could negatively influence the outcome of secondary exposure to nicotine.
2023-11-11 | GSE242791 | GEO
Project description:The long-term goal of this project is to establish whether and how chronic nicotine exposure affects nervous system function. The biological targets of nicotine action are diverse members of the superfamily of neurotransmitter-gated ion channels called nicotinic acetylcholine receptors (nAChR). nAChR play multiple, critical roles in chemical signaling throughout the brain and body. They also must be involved in nicotine dependence, which drives tobacco product use responsible for tremendous economic and personal costs. To define changes in gene expression induced by nicotine exposure in a model neuronal cell lines expressing at least two nicotinic receptor subtypes. Nicotine exposure exerst at least some of its effects on nervous system function by altering gene expression. Cells of the SH-SY5Y human neuroblastoma will be exposed to an efficacious dose of nicotine or to control medium for two different periods. Keywords: time-course
2008-04-19 | GSE11208 | GEO
Project description:Perinatal smoke/nicotine exposure alters lung development and causes asthma in exposed offspring, transmitted transgenerationally. The mechanism underlying the transgenerational inheritance of perinatal smoke/nicotine-induced asthma remains unknown, but germline epigenetic modulations may play a role. Using a well-established rat model of perinatal nicotine-induced asthma, we determined the DNA methylation pattern of spermatozoa of F1 rats exposed perinatally to nicotine in F0 gestation. To identify differentially methylated regions (DMRs), reduced representation bisulfite sequencing was performed on spermatozoa of F1 litters. The top regulated gene body and promoter DMRs were tested for lung gene expression levels, and key proteins involved in lung development and repair were determined. The overall CpG methylation in F1 sperms across gene bodies, promoters, 5’UTRs, exons, introns, and 3’UTRs was not affected by nicotine exposure. However, the methylation levels were different between the different genomic regions. 81 CpG sites, 16 gene bodies, and 3 promoter regions were differentially methylated. Gene enrichment analysis of DMRs revealed pathways involved in oxidative stress, nicotine response, alveolar and brain development, and cellular signaling. Among the DMRs, Dio1 and Nmu were the most hypermethylated and hypomethylated genes, respectively. Gene expression analysis showed that the mRNA expression and DNA methylation were incongruous. Key proteins involved in lung development and repair were significantly different (FDR < 0.05) between the nicotine and placebo-treated groups. Our data show that DNA methylation is remodeled in offspring spermatozoa upon perinatal nicotine exposure. These epigenetic alterations may play a role in transgenerational inheritance of perinatal smoke/nicotine induced asthma.
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Project description:Paternal nicotine exposure can alter phenotypes in future generations. To explore whether paternal nicotine exposure affects the hepatic repair to chronic injury which would lead to hepatic fibrosis in offspring, we establish a paternal effect model based on nicotine exposure in mice.
2020-07-31 | GSE155308 | GEO
Project description:Although it is increasingly accepted that some paternal environmental conditions can influence phenotypes in future generations, it remains unclear whether phenotypes induced in offspring represent specific responses to particular aspects of the paternal exposure history, or whether they represent a more generic response to paternal “quality of life”. To establish a paternal effect model based on a specific ligand-receptor interaction and thereby enable pharmacological interrogation of the offspring phenotype, we explored the effects of paternal nicotine administration on offspring phenotype in mouse. We show that paternal exposure to chronic nicotine induced a broad protective response to xenobiotic exposure in the next generation. This effect manifested as increased survival following an injection of toxic levels of nicotine, was specific to male offspring, and was only observed after these offspring were first acclimated to low levels of nicotine for a week. Importantly, offspring xenobiotic resistance was documented not only for toxic nicotine challenge, but also for toxic cocaine challenge, indicating that paternal nicotine exposure reprograms offspring to become broadly resistant to environmental toxins. Mechanistically, the reprogrammed state was characterized by enhanced clearance of nicotine in drug-acclimated animals, and we found that isolated hepatocytes displayed upregulation of enzymes that metabolize xenobiotics. Taken together, our data show that paternal nicotine exposure induces a protective phenotype in offspring by enhancing metabolic tolerance to xenobiotics in the environment.
2017-02-02 | GSE92240 | GEO
Project description:Nicotine intake, whether through tobacco smoking or e-cigarettes, remains a global health concern. An emerging preclinical literature indicates that parental nicotine exposure produces behavioral, physiological, and molecular changes in subsequent generations. However, the heritable effects of voluntary parental nicotine taking are unknown. Here, we show increased acquisition of nicotine taking in male and female offspring of sires that self-administered nicotine. In contrast, self-administration of sucrose and cocaine were unaltered in male and female offspring suggesting that the intergenerational effects of paternal nicotine taking may be reinforcer specific. Further characterization revealed memory deficits and increased anxiety-like behaviors in drug-naïve male, but not female, offspring of nicotine-experienced sires. Using an unbiased, genome-wide approach, we discovered that these phenotypes were associated with decreased expression of Satb2, a transcription factor known to play important roles in synaptic plasticity and memory formation, in the hippocampus of nicotine-sired male offspring. This effect was sex-specific as no changes in Satb2 expression were found in nicotine-sired female offspring. Finally, increasing Satb2 levels in the hippocampus prevented the escalation of nicotine intake and rescued the memory deficits associated with paternal nicotine taking in male offspring. Collectively, these findings indicate that paternal nicotine taking produces heritable sex-specific molecular changes that promote addiction-like phenotypes and memory impairments in male offspring. To characterize the molecular changes associated with the heritable effects of paternal nicotine taking, an unbiased, whole-genome analysis was used to characterize the hippocampal transcriptome of drug-naïve F1 males
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Project description:Paternal nicotine enhances fear memory, reduces nicotine administration and alters hippocampal genetic and neural function in offspring
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Project description:Although it is increasingly accepted that some paternal environmental conditions can influence phenotypes in future generations, it generally remains unclear whether the phenotypes induced in offspring represent specific responses to particular aspects of the paternal exposure history, or whether they represent a more generic response to paternal “quality of life”. To establish a paternal effect model based on a known ligand-receptor interaction and thereby enable pharmacological interrogation of the specificity of the offspring response, we explored the effects of paternal nicotine administration on offspring phenotype in mouse. We show that chronic paternal exposure to nicotine prior to reproduction induced a broad protective response to multiple xenobiotics in the next generation. This effect manifested as increased survival following an injection of toxic levels of either nicotine or of cocaine, was specific to male offspring, and was only observed after offspring were first acclimated to sublethal doses of nicotine or cocaine. Mechanistically, the reprogrammed state was characterized by enhanced clearance of nicotine in drug-acclimated animals, accompanied by hepatic upregulation of genes involved in xenobiotic metabolism. Surprisingly, this protective effect could also be induced by paternal exposure to a nicotinic receptor antagonist as well as to nicotine, suggesting that paternal xenobiotic exposure, rather than nicotinic receptor signaling, is likely to be responsible for programming of offspring drug resistance. Taken together, our data show that paternal drug exposure can induce a protective phenotype in offspring by enhancing metabolic tolerance to xenobiotics in the environment.
2017-02-01 | GSE94059 | GEO
Project description:The long-term goal of this project is to establish whether and how chronic nicotine exposure affects nervous system function. The biological targets of nicotine action are diverse members of the superfamily of neurotransmitter-gated ion channels called nicotinic acetylcholine receptors (nAChR). nAChR play multiple, critical roles in chemical signaling throughout the brain and body. They also must be involved in nicotine dependence, which drives tobacco product use responsible for tremendous economic and personal costs. To define changes in gene expression induced by nicotine exposure in a model neuronal cell lines expressing at least two nicotinic receptor subtypes. Nicotine exposure exerst at least some of its effects on nervous system function by altering gene expression. Cells of the SH-SY5Y human neuroblastoma will be exposed to an efficacious dose of nicotine or to control medium for two different periods.
2008-06-11 | E-GEOD-11208 | biostudies-arrayexpress
Project description:Nicotine is a common environmental pollution which is diffused into the air in the form of cigarette smoke fumes. Due to its lipophilic nature, nicotine can rapidly transport through membrane barriers and spread throughout the body which leads to abnormalities in the human brain, heart and even the fatal. However, the effects of nicotine on early embryonic development remains elusive. In this study, we found that nicotine significantly affected early embryonic development with decreased blastocyst formation. In addition, embryos treated with nicotine caused increased level of ROS, DNA damage and cell apoptosis. By RNA sequencing analysis, we demonstrated that nicotine affected the expression of placental development genes. Consistently, we found that the placental development at E17.5 was impaired by nicotine exposure, with increased placental weight and disrupted placental structure. This was due to excessive activation of the Notch signaling pathway, since blocking Notch signal by DAPT treatment recovered abnormal placental weight and structure induced by nicotine exposure. We also observed that nicotine exposure could specifically cause promoter hypermethylation of Phlda2 (a maternally expressed imprinted gene associated with placental development) and lead to its abnormal expression. Overall, this study provides evidence that nicotine causes the declining quality of early embryo and leads to placental abnormalities related with over-activation of the Notch signaling pathway.
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