title: Glucose or Altered Ceramide Biosynthesis Mediate Oxygen Deprivation Sensitivity Through Novel Pathways Revealed by Transcriptome Analysis in Caenorhabditis elegans.
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.
authors: Department of Biological Sciences, University of North Texas, Denton, Texas 76203.
authors: Mary L
authors: ML
authors: Ladage
authors: Department of Biological Sciences, University of North Texas, Denton, Texas 76203.
authors: Skylar D
authors: SD
authors: King
authors: Department of Biological Sciences, University of North Texas, Denton, Texas 76203.
authors: David J
authors: DJ
authors: Burks
authors: Department of Biological Sciences, University of North Texas, Denton, Texas 76203.
authors: Daniel L
authors: DL
authors: Quan
authors: Department of Biological Sciences, University of North Texas, Denton, Texas 76203.
authors: Anastacia M
authors: AM
authors: Garcia
authors: Department of Biological Sciences, University of North Texas, Denton, Texas 76203 Department of Mathematics, University of North Texas, Denton, Texas 76203.
authors: Rajeev K
authors: RK
authors: Azad
authors: Department of Biological Sciences, University of North Texas, Denton, Texas 76203 pamela.padilla@unt.edu.
authors: Pamela A
authors: PA
authors: Padilla
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002518:Ceramides / Q000096:biosynthesis*; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D005947:Glucose / Q000096:biosynthesis*; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D050216:Metabolic Detoxication, Phase I / Q000235:genetics; D050217:Metabolic Detoxication, Phase II / Q000235:genetics; D009154:Mutation; D010100:Oxygen / Q000378:metabolism*; D010641:Phenotype; D015398:Signal Transduction; D059467:Transcriptome; D015262:Xenobiotics / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D002518:Ceramides; D015262:Xenobiotics; D005947:Glucose; D010100:Oxygen
keywords: collagen; glucose toxicity; innate immunity; lipid biosynthesis; xenobiotic and endobiotic detoxification