Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of mouse liver genomic responses to ciguatoxin (P-CTX-1)

ABSTRACT: Ciguatoxins (CTX) are polyether neurotoxins responsible for ciguatera, the most common fish-borne food poisoning in humans. This study characterizes the global transcriptional response of mouse liver to a symptomatic dose (0.26 ng/g) of the highly potent Pacific ciguatoxin-1 (P-CTX-1). At 1 h post exposure 2.4% of features on a 44K whole genome array were differentially expressed (p â?¤ 0.0001), increasing to 5.2% at 4 h and decreasing to 1.4% by 24 h post-CTX exposure. Early gene expression was likely influenced prominently by an acute 4 Â°C decline in core body temperature by 1 h, which resolved by 8 h following exposure. Cytochrome P450s were of particular interest due to their role in xenobiotic metabolism. Twenty-seven genes, mostly members of Cyp2 and Cyp4 families, showed significant changes in expression. Many Cyps underwent an initial down-regulation at 1 h but were quickly and strongly up-regulated at 4 and 24 h post exposure. In addition to Cyps, increases in several glutathione S-transferases were observed, an indication that both phase I and phase II metabolic reactions are involved in the hepatic response to CTX in mice. Experiment Overall Design: Individual C57/BL6 mice (n=3) exposed to 0.26 ng/g P-CTX-1 ip for 1, 4, or 24 h were compared to pooled time-matched controls (n=3). The triplicate arrays at each time point included a dye swap.

ORGANISM(S): Mus musculus

SUBMITTER: Frances Van Dolah

PROVIDER: E-GEOD-10768 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Liver genomic responses to ciguatoxin: evidence for activation of phase I and phase II detoxification pathways following an acute hypothermic response in mice.

Morey Jeanine S JS Ryan James C JC Bottein Dechraoui Marie-Yasmine MY Rezvani Amir H AH Levin Edward D ED Gordon Christopher J CJ Ramsdell John S JS Van Dolah Frances M FM

Toxicological sciences : an official journal of the Society of Toxicology 20080318 2

Ciguatoxins (CTX) are polyether neurotoxins that target voltage-gated sodium channels and are responsible for ciguatera, the most common fish-borne food poisoning in humans. This study characterizes the global transcriptional response of mouse liver to a symptomatic dose (0.26 ng/g) of the highly potent Pacific ciguatoxin-1 (P-CTX-1). At 1 h post-exposure 2.4% of features on a 44K whole genome array were differentially expressed (p < or = 0.0001), increasing to 5.2% at 4 h and decreasing to 1.4% ...[more]

PMID: 18353800

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Project description:The cellular microRNA, miR-155 has been shown to be involved in lymphocyte activation and is expressed in EBV infected cells displaying type III latency gene expression but not type I latency gene expression. We show here that the elevated levels of miR-155 in type III latency cells is due to EBV gene expression and not epigenetic differences in cell lines tested and we show that expression in EBV infected cells requires a conserved AP-1 element in the miR-155 promoter. Gene expression analysis was carried out in a type I latency cell line transduced with a miR-155 expressing retrovirus. This analysis identified both miR-155 suppressed and induced cellular mRNAs and suggested that in addition to direct targeting of 3’ UTRs, miR-155 alters gene expression in part through the alteration of signal transduction pathways. 3’ UTR reporter analysis of predicted miR-155 target genes identified the transcriptional regulatory genes, BACH1, ZIC3, HIVEP2, CEBPB, ZNF652, ARID2, and SMAD5 as miR-155 targets. Western blot analysis of the most highly suppressed of these, BACH1, showed lower expression in cells transduced with a miR-155 retrovirus. Inspection of the promoters from genes regulated in EBV infected cells and in cells infected with a miR-155 retrovirus identified potential binding sequences for BACH1 and ZIC3. Together, these experiments suggest that the induction of miR-155 by EBV contributes to EBV mediated signaling in part through the modulation of transcriptional regulatory factors. Keywords: Differential expression of miR-155 vs cntl expressing cells The EBV positive Burkitt's lymphoma cell line, Akata was infected with a control (pEhyg-miRCntl) or a microRNA-155 expressing (pEhyg-miR-155) retrovirus. Duplicate infections with the control retrovirus and with the miR-155 retrovirus were carried out. Control and miR-155 infection pair 1 were run on an array as well as a dye swap. Control and miR-155 infection pair 2 were similarly run on an array as well as a second array containing a dye swap.

Dataset Information

Transcription profiling of mouse liver genomic responses to ciguatoxin (P-CTX-1)

Publications

Liver genomic responses to ciguatoxin: evidence for activation of phase I and phase II detoxification pathways following an acute hypothermic response in mice.

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