RRC ID 53312
Author Ladage ML, King SD, Burks DJ, Quan DL, Garcia AM, Azad RK, Padilla PA.
Title Glucose or Altered Ceramide Biosynthesis Mediate Oxygen Deprivation Sensitivity Through Novel Pathways Revealed by Transcriptome Analysis in Caenorhabditis elegans.
Journal G3 (Bethesda)
Abstract Individuals with type 2 diabetes display metabolic abnormalities, such as hyperglycemia, increased free fatty acids, insulin resistance, and altered ceramide levels, that contribute to vascular dysfunctions and compromised oxygen delivery. Caenorhabditis elegans fed a glucose-supplemented diet or with altered ceramide metabolism, due to a hyl-2 mutation, are sensitive to oxygen deprivation (anoxia). Our experiments showed that the combination of these factors further decreased the anoxia survival. RNA-sequencing analysis was performed to assess how a glucose-supplemented diet and/or a hyl-2 mutation altered the transcriptome. Comparison analysis of transcripts associated with anoxia-sensitive animals [hyl-2(tm2031) mutation or a glucose diet] revealed 199 common transcripts encoded by genes with known or predicted functions involving innate immunity, cuticle function (collagens), or xenobiotic and endobiotic phase I and II detoxification system. Use of RNA interference (RNAi) to target gene products of the xenobiotic and endobiotic phase I and II detoxification system (UDP-glycosyltransferase and Cytochrome p450 genes; ugt-15, ugt-18, ugt-19, ugt-41, ugt-63, cyp-13A12, cyp-25A1, and cyp-33C8) increased anoxia survival in wild-type animals fed a standard diet. Anoxia sensitivity of the hyl-2(tm2031) animals was suppressed by RNAi of cyp-25A1 or cyp-33C8 genes. A glucose diet fed to the P0 hermaphrodite decreased the anoxia survival of its F1 embryos; however, the RNAi of ugt-63 and cyp-33C8 suppressed anoxia sensitivity. These studies provide evidence that the detoxification system impacts oxygen deprivation responses and that C. elegans can be used to model the conserved detoxification system.
Volume 6(10)
Pages 3149-3160
Published 2016-10-13
DOI 10.1534/g3.116.031583
PII g3.116.031583
PMID 27507791
PMC PMC5068937
MeSH Animals Caenorhabditis elegans / genetics* Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Ceramides / biosynthesis* Cluster Analysis Computational Biology / methods Gene Expression Profiling* Gene Knockdown Techniques Glucose / biosynthesis* Hypoxia / genetics Hypoxia / metabolism Lipid Metabolism Male Metabolic Detoxication, Phase I / genetics Metabolic Detoxication, Phase II / genetics Mutation Oxygen / metabolism* Phenotype Signal Transduction* Transcriptome* Xenobiotics / metabolism
IF 2.781
Times Cited 8
C.elegans tm2031