Correction: The Transcriptional Response of Caenorhabditis elegans to Ivermectin Exposure Identifies Novel Genes Involved in the Response to Reduced Food Intake

AbstractRecently, we reported that, in mice, hunger causes the autophagy-dependent release of a protein called “acyl-CoA-binding protein” or “diazepam binding inhibitor” (ACBP/DBI) from cells, resulting in an increase in plasma ACBP concentrations. Administration of extra ACBP is orexigenic and obesogenic, while its neutralization is anorexigenic in mice, suggesting that ACBP is a major stimulator of appetite and lipo-anabolism. Accordingly, obese persons have higher circulating ACBP levels than lean individuals, and anorexia nervosa is associated with subnormal ACBP plasma concentrations. Here, we investigated whether ACBP might play a phylogenetically conserved role in appetite stimulation. We found that extracellular ACBP favors sporulation in Saccharomyces cerevisiae, knowing that sporulation is a strategy for yeast to seek new food sources. Moreover, in the nematode Caenorhabditis elegans, ACBP increased the ingestion of bacteria as well as the frequency pharyngeal pumping. These observations indicate that ACBP has a phylogenetically ancient role as a ‘hunger factor’ that favors food intake.

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Measuring Food Intake and Nutrient Absorption in Caenorhabditis elegans

Genetics ◽

10.1534/genetics.115.175851 ◽

2015 ◽

Vol 200 (2) ◽

pp. 443-454 ◽

Cited By ~ 49

Author(s):

Rafael L. Gomez-Amaro ◽

Elizabeth R. Valentine ◽

Maria Carretero ◽

Sarah E. LeBoeuf ◽

Sunitha Rangaraju ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Food Intake ◽

Nutrient Absorption

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Characterization of the xenobiotic response of Caenorhabditis elegans to the anthelmintic drug albendazole and the identification of novel drug glucoside metabolites

Biochemical Journal ◽

10.1042/bj20101346 ◽

2010 ◽

Vol 432 (3) ◽

pp. 505-516 ◽

Cited By ~ 41

Author(s):

Steven T. Laing ◽

Al Ivens ◽

Roz Laing ◽

Sai Ravikumar ◽

Victoria Butler ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Stress Responses ◽

Transcriptional Response ◽

Metabolizing Enzymes ◽

C Elegans ◽

Genes Encoding ◽

Minimal Importance ◽

Xenobiotic Response ◽

Novel Drug ◽

Anthelmintic Drugs

Knowledge of how anthelmintics are metabolized and excreted in nematodes is an integral part of understanding the factors that determine their potency, spectrum of activity and for investigating mechanisms of resistance. Although there is remarkably little information on these processes in nematodes, it is often suggested that they are of minimal importance for the major anthelmintic drugs. Consequently, we have investigated how the model nematode Caenorhabditis elegans responds to and metabolizes albendazole, one of the most important anthelmintic drugs for human and animal use. Using a mutant strain lacking the β-tubulin drug target to minimize generalized stress responses, we show that the transcriptional response is dominated by genes encoding XMEs (xenobiotic-metabolizing enzymes), particularly cytochrome P450s and UGTs (UDP-glucuronosyl transferases). The most highly induced genes are predominantly expressed in the worm intestine, supporting their role in drug metabolism. HPLC-MS/MS revealed the production of two novel glucoside metabolites in C. elegans identifying a major difference in the biotransformation of this drug between nematodes and mammals. This is the first demonstration of metabolism of a therapeutic anthelmintic in C. elegans and provides a framework for its use to functionally investigate nematode anthelmintic metabolism.

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Remodeling of the Caenorhabditis elegans non-coding RNA transcriptome by heat shock

Nucleic Acids Research ◽

10.1093/nar/gkz693 ◽

2019 ◽

Vol 47 (18) ◽

pp. 9829-9841 ◽

Cited By ~ 6

Author(s):

William P Schreiner ◽

Delaney C Pagliuso ◽

Jacob M Garrigues ◽

Jerry S Chen ◽

Antti P Aalto ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Heat Shock ◽

Elevated Temperatures ◽

Transcriptional Response ◽

Heat Shock Factor 1 ◽

Protein Coding ◽

Repeat Elements ◽

Cellular Survival ◽

Non Coding Rna ◽

Shock Proteins

Abstract Elevated temperatures activate a heat shock response (HSR) to protect cells from the pathological effects of protein mis-folding, cellular mis-organization, organelle dysfunction and altered membrane fluidity. This response includes activation of the conserved transcription factor heat shock factor 1 (HSF-1), which binds heat shock elements (HSEs) in the promoters of genes induced by heat shock (HS). The upregulation of protein-coding genes (PCGs), such as heat shock proteins and cytoskeletal regulators, is critical for cellular survival during elevated temperatures. While the transcriptional response of PCGs to HS has been comprehensively analyzed in a variety of organisms, the effect of this stress on the expression of non-coding RNAs (ncRNAs) has not been systematically examined. Here we show that in Caenorhabditis elegans HS induces up- and downregulation of specific ncRNAs from multiple classes, including miRNA, piRNA, lincRNA, pseudogene and repeat elements. Moreover, some ncRNA genes appear to be direct targets of the HSR, as they contain HSF-1 bound HSEs in their promoters and their expression is regulated by this factor during HS. These results demonstrate that multiple ncRNA genes respond to HS, some as direct HSF-1 targets, providing new candidates that may contribute to organismal survival during this stress.

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