Chronic Ethanol Exposure Increases Cytochrome P‐450 and Decreases Activated in Blocked Unfolded Protein Response Gene Family Transcripts in Caenorhabditis elegans

Abstract

Ethanol is a widely consumed and rapidly absorbed toxin. While the physiological effects of ethanol consumption are well known, the underlying biochemical and molecular changes at the gene expression level in whole animals remain obscure. We exposed the model organism Caenorhabditis elegans to 0.2 M ethanol from the embryo to L4 larva stage and assayed gene expression changes in whole animals using RNA-Seq and quantitative real-time PCR. We observed gene expression changes in 1122 genes (411 up, 711 down). Cytochrome P-450 (CYP) gene family members (12 of 78) were upregulated, whereas activated in blocked unfolded protein response (ABU) (7 of 15) were downregulated. Other detoxification gene family members were also regulated including four glutathione-S-transferases and three flavin monooxygenases. The results presented show specific gene expression changes following chronic ethanol exposure in C. elegans that indicate both persistent upregulation of detoxification response genes and downregulation of endoplasmic reticulum stress pathway genes.

The Genetics of Alcohol Responses of Invertebrate Model Systems

“…HSP70 is induced by stress and is thought to function as a chaperone (Hranitz, Abramson, & Carter, 2010). In C. elegans, chronic ethanol exposure leads to an induction of a cytochrome p450 family of genes that are highly inducible by a wide range of environmental toxins (Peltonen, Aarnio, Heikkinen, Lakso, & Wong, 2013). In addition, the C. elegans seb-3 gene, which encodes a CRF receptor-like GPCR that regulates arousal state and heat-shock stress responses, has also been implicated in ethanol responses.…”

JMJD-1.2/PHF8 controls axon guidance by regulating Hedgehog-like signaling

“…Barcode and adaptor-cleaned sequences were checked for quality using FastQC (Babraham Bioinformatics) and mapped to the C. elegans genome (WS220) with TopHat 2.0.9 (Trapnell et al, 2012) using parameters described previously (Peltonen et al, 2013). Reads successfully mapped were >95% using a criterion of two mismatches.…”

Impaired removal of H3K4 methylation affects cell fate determination and gene transcription

“…Bar code and adaptor-cleaned sequences were checked for quality using FastQC and mapped to the C. elegans genome (WS220) with TopHat 2.0.9 (Trapnell et al, 2012) using parameters as described previously (Peltonen et al, 2013). Reads successfully mapped was ∼50% using a criteria of two mismatches.…”