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8-oxoG RNA IP data set 1: Air pollution mixture derived from the reaction of 790 ppb acrolein, 670 ppb methacrolein, and 4 ppm O3 for 1.5 h

ABSTRACT: While environmental agents such as air pollution have been shown to be causative to diseases, yet limited knowledge exist on their mechanism of action. Here we used RNA-sequencing in combination with specific immunoprecipitation of 8-oxo-7,8-dihydroguanosine (8-oxoG) to identify transcripts accumulating oxidation after exposure to air pollution (derived from the reaction of 790 ppb acrolein, 670 ppb methacrolein, and 4 ppm ozone) in bronchial epithelial BEAS-2B cells. Results from this analysis suggest a functional role of the 8-oxoG modified transcripts after air pollution exposure in pathways that are central regulators of cell metabolism, growth, proliferation and maintenance of cellular structure. This study highlights a critical role for a RNA epitranscriptomics modification that can be used to further characterize biological responses to external stressors once considered indistinguishable.

ORGANISM(S): Homo sapiens

PROVIDER: GSE123933 | GEO | 2020/07/27

REPOSITORIES: GEO

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8-oxoG RNA IP data set 2: Air pollution mixture derived from the reaction of 100 ppb acrolein, 97 ppb methacrolein, 44 ppb alpha-pinene and 100 ppb O3 for 1.5 h

Project description:While environmental agents such as air pollution have been shown to be causative to diseases, yet limited knowledge exist on their mechanism of action. Here we used RNA-sequencing in combination with specific immunoprecipitation of 8-oxo-7,8-dihydroguanosine (8-oxoG) to identify transcripts accumulating oxidation after exposure to air pollution (derived from the reaction of acrolein, methacrolein, alpha-pinene and ozone) in bronchial epithelial BEAS-2B cells. Results from this analysis suggest a functional role of the 8-oxoG modified transcripts after air pollution exposure in pathways that are central regulators of cell metabolism, growth, proliferation and maintenance of cellular structure. This study highlights a critical role for a RNA epitranscriptomics modification that can be used to further characterize biological responses to external stressors once considered indistinguishable.

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8-oxoG RNA IP data set 1: Air pollution mixture derived from the reaction of 790 ppb acrolein, 670 ppb methacrolein, and 4 ppm O3 for 1.5 h

Project description:8-oxoG RNA IP data set 1: Air pollution mixture derived from the reaction of 790 ppb acrolein, 670 ppb methacrolein, and 4 ppm O3 for 1.5 h

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8-oxoG RNA IP data set 2: Air pollution mixture derived from the reaction of 100 ppb acrolein, 97 ppb methacrolein, 44 ppb alpha-pinene and 100 ppb O3 for 1.5 h

Project description:8-oxoG RNA IP data set 2: Air pollution mixture derived from the reaction of 100 ppb acrolein, 97 ppb methacrolein, 44 ppb alpha-pinene and 100 ppb O3 for 1.5 h

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Acrolein-induced transcriptomic alterations in male Wistar-Kyoto rats

Project description:Acute acrolein inhalation in male rats resulted in multi-tissue transcriptomic alterations that were observed through Illumina mRNA sequencing. Specifically, site-specific respiratory expression profile differences were noted between air- and acrolein-exposed groups. Nasal epithelial tissue demonstrated 452 differentially expressed genes (DEGs) (310 up-regulated and 142 down-regulated)and lung tissue demonstrated 95 DEGs (80 up-regulated and 15 down-regulated). Notable transcriptomic alterations were also observed in liver tissue of acrolein-exposed rats, with 1699 identified DEGs (788 up-regulated and 911 down-regulated). A variety of mRNA expression profile differences resulting from acute acrolein inhalation was observed in other peripheral tissues, including adipose, muscle, adrenals, hippocamus, and hypothalamus. Gene changes were largely representative of oxidative and inflammatory response in the nose, as well as xenobiotic metabolism changes in the lung. Liver changes, which were most numerous, included alterated metabolic signaling (Sirtuin and FXR signaling), as well as alterated oxidoreductive, GPCR, and glucocorticoid pathways. Together, these data demonstrate acrolein, a well-characterized respiratory irritant, induces systemic neuroendocrine immunological and metabolic stress.

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Identification of 8-oxoG binding proteins in Deinococcus radiodurans

Project description:8-oxo-7,8-dihydroguanine (8-oxoG) is a common RNA oxidation that has been implicated in carcinogenesis, neurodegeneration, and aging. Some? Many? RNA-binding proteins have shown binding preference for 8-oxoG modified RNA; such binding? can protect cells from oxidative stress. To date, the presence of specific 8-oxoG-recognizing proteins is only known in model organisms, but, how these proteins cooperate is still unclear. Here, we use RNA affinity chromatography and mass spectrometry to search for proteins that specifically bind 8-oxoG-modified RNA in Deinococcus radiodurans, an extremophilic bacterium with extraordinary resistance to oxidative stresses. We identified four proteins that selectively bind to oxidized RNA: polynucleotide phosphorylase (DR_2063/PNPase), ATP-dependent DEAD-box RNA helicase (DR_0335/RhlB), ribosomal protein S1 (DR_1983/RpsA), and transcriptional termination factor (DR_1338/Rho). The knockout of PNPase and RhlB in D. radiodurans caused increased sensitivity to hydrogen peroxide and a significant accumulation of 8-oxoG modified RNA. Importantly, PNPase directly interacts with RhlB in D. radiodurans; however, no additional phenotypic effect was observed for the double deletion of pnp and rhlB compared to the individual single deletions. Overall, our findings suggest a role of the PNPase-RhlB complex in targeting 8-oxoG-modified RNAs for rapid degradation and thereby constitutes an important component of D. radiodurans resistance to oxidative stress.

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Acrolein-mediated changes in HUVEC miRNA

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Transcription profiling of mouse T cell sub-populations isolated from pulmonary tissue after mice were exposured to filtered air of acrolein for one week

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Combining RNA-Sequencing with immunoprecipitation of 8-oxo-7,8-dihydroguanosine (8-oxoG) facilitates discovery of cellular effects associated with lung cell exposure to air pollution

Project description:Combining RNA-Sequencing with immunoprecipitation of 8-oxo-7,8-dihydroguanosine (8-oxoG) facilitates discovery of cellular effects associated with lung cell exposure to air pollution

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Next Generation Sequencing Facilitates Quantitative Analysis of Wildtype, akr1a1a-/- and Wildtype with Acrolein Treatment Zebrafish Larvae Transcriptomes

Project description:Our previous experiments showed the function of Akr1a1a was related to insulin resistance. The knockout of Akr1a1a led to poor acrolein detoxification and accumulated acrolein inhibits insulin receptors (insra/insrb) expression. To understand how the loss of Akr1a1a and acrolein reflects at the transcriptome level, we performed full genome RNA-Seq between akr1a1a+/+, akr1a1a-/- and akr1a1a+/+ with acrolein treatment zebrafish larvae at 120 hpf. An overview of RNA-Seq, including quality control, principal component analysis (PCA), and volcano plots of regulated genes showed comparable properties between akr1a1a mutants, wild type and acrolein treated wild type zebrafish larvae. We found the insulin receptor signaling pathway was down-regulated significantly in akr1a1a mutants and acrolein treated wild type larvae as compared to wild type larvae via gene set enrichment analysis (normalized enrichment score, -1.888, p=0.028; -1.93, p=0.019). Intriguingly, downstream signaling pathways including MAPK, signal transduction by protein phosphorylation and transmembrane receptor protein tyrosine kinase signaling pathway were also significantly down-regulated in akr1a1a mutants and acrolein treated wild type larvae. Taken together, these results further suggest akr1a1a and acrolein as an important regulator in insulin receptor signaling transduction. Furthermore, we offer a comprehensive and more detailed evaluation of mRNA content within zebrafish larvae. We conclude that RNA-seq based transcriptome would clearly illustrate genetic network and clarify complex biological functions.

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