Identification of novel ethanol-sensitive genes by expression profiling

Rahman, Sajida; Miles, Michael F.

doi:10.1016/s0163-7258(01)00163-2

Cited by 24 publications

(15 citation statements)

References 69 publications

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“…Of these, the cluster showing the largest and most significant enrichment included 38 genes that participate in ribosome biosynthesis including 27 large and 11 small ribosomal subunit proteins, as well as two additional participants in ribosome biogenesis, pescadillo (PES-1, 1.198-fold) and NSA2 (1.340-fold). Two separate interrogations of mouse neural folds, 3–4hr post-ethanol treatment, have each found significant decreases in ribosome transcripts (Downing et al 2012; Green et al 2007), as have studies of ethanol-treated neuronal cultures (Rahman and Miles, 2001; Gutala et al, 2004). Our own preliminary findings have similarly identified ribosome biogenesis as the most significantly altered gene cluster in these chick neuroprogenitors 6hr post-ethanol challenge (ME Berres, A Garic, SM Smith, unpublished).…”

Section: Discussionmentioning

confidence: 87%

High-Throughput Transcriptome Sequencing Identifies Candidate Genetic Modifiers of Vulnerability to Fetal Alcohol Spectrum Disorders

Garic

Berres

Smith

2014

Alcohol Clin Exp Res

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Introduction FASD is a leading cause of neurodevelopmental disability. Genetic factors can modify vulnerability to FASD, but these elements are poorly characterized. Methods We performed high-throughput transcriptional profiling to identify gene candidates that could potentially modify vulnerability to ethanol’s neurotoxicity. We interrogated a unique genetic resource, neuroprogenitor cells from two closely-related Gallus gallus lines having well-characterized robust or attenuated ethanol responses with respect to intracellular calcium mobilization and CaMKII / β-catenin-dependent apoptosis. Samples were not exposed to ethanol prior to analysis. Results We identified 363 differentially expressed genes in neuroprogenitors from these two lines. KEGG analysis revealed several gene clusters having significantly differential enrichment in gene expression. The largest and most significant cluster comprised ribosomal proteins (38 genes, p = 1.85 × 10−47). Other significantly enriched gene clusters included metabolism (25 genes, p = 0.0098), oxidative phosphorylation (18 genes, p = 1.10 × 10−11), spliceosome (13 genes, p = 7.02 × 10−8) and protein processing in the endoplasmic reticulum (9 genes, p = 0.0011). Inspection of GO-terms identified 24 genes involved in the calcium/β-catenin signals that mediate ethanol's neurotoxicity in this model, including β-catenin itself and both calmodulin isoforms. Conclusions Four of the identified pathways with altered transcript abundance mediate the flow of cellular information from RNA to protein. Importantly, ribosome biogenesis also senses nucleolar stress and regulates p53-mediated apoptosis in neural crest. Human ribosomopathies produce craniofacial malformations and eleven known ribosomopathy genes were differentially expressed in this model of neural crest apoptosis. Rapid changes in ribosome expression are consistently observed in ethanol-treated mouse embryo neural folds, a model that is developmentally similar to ours. The recurring identification of ribosome biogenesis suggests it is a candidate modifier of ethanol vulnerability. These results highlight this approach’s efficacy to formulate new, mechanistic hypotheses regarding ethanol’s developmental damage.

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Section: Discussionmentioning

confidence: 87%

High-Throughput Transcriptome Sequencing Identifies Candidate Genetic Modifiers of Vulnerability to Fetal Alcohol Spectrum Disorders

Garic

Berres

Smith

2014

Alcohol Clin Exp Res

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“…Microarray studies have been performed to elucidate genes that regulate acute responses to ethanol (Kerns et al 2005;Kwon et al 2004) that underlie genetic differences in inbred and selected lines of rodents (Edenberg et al 2004;Saito et al 2004, Spence et al 2005Thibault et al 2000), the effects of chronic ethanol treatment or withdrawal in rodents and worms (Daniels and Buck 2002;Kwon et al 2004;Rimondini et al 2002Saito et al 2002, and the effects of long-term alcohol use in humans (Flatscher-Bader et al 2005;Lewohl et al 2000;Mayfield et al 2002). These studies varied in experimental design (for review see Rahman and Miles 2001;Worst and Vrana 2005). Daniels and Buck (2002) observed decreased expression of transthyretin during withdrawal from chronic ethanol inhalation in the hippocampus from C57BL/6J mice, but there were no other commonalities between the results presented here and previous studies.…”

Section: Transthyretin and Chronic Ethanol Treatmentmentioning

confidence: 99%

Microarray Analysis of the Effects of a γ-protein Kinase C Null Mutation on Gene Expression in Striatum: A Role for Transthyretin in Mutant Phenotypes

Smith

Bowers²,

Radcliffe

et al. 2006

Behav Genet

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A constitutive null mutation of the neural-specific isotype of protein kinase C (gamma-PKC) in mice produces alterations in behavioral traits and responses to ethanol suggesting that gamma-PKC-mediated phosphorylation is essential for regulation of some behaviors. However, it is possible that some of the effects of gamma-PKC gene deletion also may be due to altered gene expression. To examine alterations in gene expression, microarray analyses were performed on striatal tissue from wild types and mutants. A total of 143 genes and ESTs were identified as potential candidates related to differences between null mutants and wild types. Confirmation studies using qRT-PCR indicated that the expression of transthyretin was increased about 8-fold in striatum of naïve mutants compared to wild types. The effect of chronic ethanol treatment on transthyretin expression was analyzed because gamma-PKC mutants do not develop tolerance to chronic ethanol treatment. Ethanol treatment of mutants reversed the dramatic increase in transthyretin expression seen in naïve and control-diet treated mutants, but did not affect transthyretin expression in wild types.

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“…Microarray analysis of cultured neural cells (SH-SY5Y neuroblastoma cells) showed that ethanol exposure altered the expression of genes involved in cyclic AMP (cAMP)/protein kinase A (PKA) signaling and norepinephrine production, as well as in oxidative stress and protein synthesis [14, 15]. In the nematode, ethanol exposure rapidly induced a cellular stress response (heat shock protein genes) [16].…”

Section: Introductionmentioning

confidence: 99%

Gene Expression Under the Influence: Transcriptional Profiling of Ethanol in the Brain

Contet

2012

CPSP

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Sensitivity to ethanol intoxication, propensity to drink ethanol and vulnerability to develop alcoholism are all influenced by genetic factors. Conversely, exposure to ethanol or subsequent withdrawal produce gene expression changes, which, in combination with environmental variables, may participate in the emergence of compulsive drinking and relapse. The present review offers an integrated perspective on brain gene expression profiling in rodent models of predisposition to differential ethanol sensitivity or consumption, in rats and mice subjected to acute or chronic ethanol exposure, as well as in human alcoholics. The functional categories over-represented among differentially expressed genes suggest that the transcriptional effects of chronic ethanol consumption contribute to the neuroplasticity and neurotoxicity characteristic of alcoholism. Importantly, ethanol produces distinct transcriptional changes within the different brain regions involved in intoxication, reinforcement and addiction. Special emphasis is put on recent profiling studies that have provided some insights into the molecular mechanisms potentially mediating genome-wide regulation of gene expression by ethanol. In particular, current evidence for a role of transcription factors, chromatin remodeling and microRNAs in coordinating the expression of large sets of genes in animals predisposed to excessive ethanol drinking or exposed to protracted abstinence, as well as in human alcoholics, is presented. Finally, studies that have compared ethanol with other drugs of abuse have highlighted common gene expression patterns that may play a central role in drug addiction. The availability of novel technologies and a focus on mechanistic approaches are shaping the future of ethanol transcriptomics.

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Identification of novel ethanol-sensitive genes by expression profiling

Cited by 24 publications

References 69 publications

High-Throughput Transcriptome Sequencing Identifies Candidate Genetic Modifiers of Vulnerability to Fetal Alcohol Spectrum Disorders

High-Throughput Transcriptome Sequencing Identifies Candidate Genetic Modifiers of Vulnerability to Fetal Alcohol Spectrum Disorders

Microarray Analysis of the Effects of a γ-protein Kinase C Null Mutation on Gene Expression in Striatum: A Role for Transthyretin in Mutant Phenotypes

Gene Expression Under the Influence: Transcriptional Profiling of Ethanol in the Brain

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