title: Genomic analyses reveal a conserved glutathione homeostasis pathway in the invertebrate chordate Ciona intestinalis.
abstract: The major thiol redox buffer glutathione (l-gamma-glutamyl-l-cysteinylglycine, GSH) is central to cell fate determination, and thus, associated metabolic and regulatory pathways are exquisitely sensitive to a wide range of environmental cues. An imbalance of cellular redox homeostasis has emerged as a pathologic hallmark of a diverse range of human gene-environment disorders. Despite the central importance of GSH in cellular homeostasis, underlying genetic regulatory pathways remain poorly defined. This report describes the annotation and expression analysis of genes contributing to GSH homeostasis in the invertebrate chordate Ciona intestinalis. A core pathway comprising 19 genes contributing to the biosynthesis of GSH and its use as both a redox buffer and a conjugate in phase II detoxification as well as known transcriptional regulators were analyzed. These genes exhibit a high level of sequence conservation with corresponding human, rat, and mouse homologs and were expressed constitutively in tissues of adult animals. The GSH biosynthetic genes Gclc and Gclm were also responsive to the prototypical antioxidant tert-butylhydroquinone. The present evidence of a conserved GSH homeostasis pathway in C. intestinalis together with its phylogenetic position as a basal chordate and lifestyle as a filter feeder constantly exposed to natural marine toxins introduces this species as an important animal model for defining molecular mechanisms that potentially underlie genetic susceptibility to environmentally associated stress.
authors.affiliation: Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
authors.forename: Gerardo M
authors.initials: GM
authors.lastname: Nava
authors.forename: David Y
authors.initials: DY
authors.lastname: Lee
authors.forename: Javier H
authors.initials: JH
authors.lastname: Ospina
authors.forename: Shi-Ying
authors.initials: SY
authors.lastname: Cai
authors.forename: H Rex
authors.initials: HR
authors.lastname: Gaskins
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002938:Ciona intestinalis / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D020869:Gene Expression Profiling; D023281:Genomics / Q000379:methods*; D005721:Glutamate-Cysteine Ligase / Q000145:classification / Q000235:genetics; D005978:Glutathione / Q000096:biosynthesis / Q000378:metabolism*; D006706:Homeostasis / Q000235:genetics*; D008969:Molecular Sequence Data; D010802:Phylogeny; D021122:Protein Subunits / Q000145:classification / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics
chemical_list: D021122:Protein Subunits; D014157:Transcription Factors; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione