Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of Puga- tBHQ and arsenic treated GCLM-WT and KO mice

ABSTRACT: Evaluate the protective effect of prior tBHQ treatment from arsenic damage at two dosage levels of arsenic (2 and 20 uM), and compare to the effect of tBHQ or arsenic treatment given alone.

ORGANISM(S): Mus musculus

SUBMITTER: Alvaro Puga

PROVIDER: E-MEXP-371 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Butylhydroquinone protects cells genetically deficient in glutathione biosynthesis from arsenite-induced apoptosis without significantly changing their prooxidant status.

Kann Simone S Estes Cameron C Reichard John F JF Huang Ming-Ya MY Sartor Maureen A MA Schwemberger Sandy S Chen Ying Y Dalton Timothy P TP Shertzer Howard G HG Xia Ying Y Puga Alvaro A

Toxicological sciences : an official journal of the Society of Toxicology 20050713 2

Arsenic, first among the top environmentally hazardous substances, is associated with skin, lung, liver, kidney, prostate, and bladder cancer. Arsenic is also a cardiovascular and a central nervous system toxicant, and it has genotoxic and immunotoxic effects. Paradoxically, arsenic trioxide is used successfully in the treatment of acute promyelocytic leukemia and multiple myeloma. Arsenic induces oxidative stress, and its toxicity is decreased by free thiols and increased by glutathione depleti ...[more]

PMID: 16014739

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Project description:We identified a novel paralog of the antioxidant response element transcription factor, Nrf2 in zebrafish. To determine whether the paralogs Nrf2a and Nrf2b regulate different sets of genes, we performed loss-of-function experiments followed by microarray-based gene expression profiling, performed on embryos in which expression of Nrf2a, Nrf2b, or both paralogs was knocked down. Embryos at the 1-4 cell stage were injected with 3-5 nl of a control morpholino (MO) or gene-specific MO to knockdown Nrf2a, Nrf2b, or a Nrf2a+b combination. At 48 hpf, triplicate groups of 5 embryos were exposed to 2 M-BM-5M of tert butyl hydroquinone or 2% DSMO for 4 hours. At 52 hpf, embryos were fixed in RNA Later and stored at -80M-BM-0C. RNA was extracted, bioanalyzed, labeled with Cy3 and hybridized to the Agilent V3 4x44K zebrafish microarray (cat. #G2519F-026437) at the Genome Technology Core of the Whitehead Institute (Cambridge, MA). Raw array data obtained from the Whitehead Institute were extracted using Agilent's feature extraction software using background detrending (spatial and multiplicative).Prior to normalization, Cy3 values below 5 were set to 5. The data were then normalized using the non-linear scaling method based on rank invariant probes. After normalization but before statistical analyses, probes not significantly above background in all microarrays were removed (3147 probes in all; based on AgilentM-bM-^@M-^Ys 2.6 standard deviation method). None of the probes were saturated for Cy3 signal on any microarray, so no further filtering was applied. There were a total of 40,456 probes for statistical analyses. Statistical tests were performed using MeV v4. Data were log transformed and median centered for each probe. An ANOVA was run for morpholino injection, with p-value based on 1000 permutations of the data and alpha of 0.01. The probes found significant in the ANOVA were subsequently examined using Rank Product (RP) analysis to identify probes up- and down-regulated by the MO injection For each RP test, a two-class unpaired RP analysis was performed using 100 permutations of the data with a false discovery rate (FDR) M-bM-^IM-$10%.

Dataset Information

Transcription profiling of Puga- tBHQ and arsenic treated GCLM-WT and KO mice

Publications

Butylhydroquinone protects cells genetically deficient in glutathione biosynthesis from arsenite-induced apoptosis without significantly changing their prooxidant status.

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