title: Alteration of the serum N-glycome of mice locally exposed to high doses of ionizing radiation.
abstract: Exposure of the skin to ionizing radiation leads to characteristic reactions that will often turn into a pathophysiological process called the cutaneous radiation syndrome. The study of this disorder is crucial to finding diagnostic and prognostic bioindicators of local radiation exposure or radiation effects. It is known that irradiation alters the serum proteome content and potentially post-translationally modifies serum proteins. In this study, we investigated whether localized irradiation of the skin alters the serum glycome. Two-dimensional differential in-gel electrophoresis of serum proteins from a man and from mice exposed to ionizing radiation showed that potential post-translational modification changes occurred following irradiation. Using a large-scale quantitative mass-spectrometry-based glycomic approach, we performed a global analysis of glycan structures of serum proteins from non-irradiated and locally irradiated mice exposed to high doses of γ-rays (20, 40, and 80 Gy). Non-supervised descriptive statistical analyses (principal component analysis) using quantitative glycan structure data allowed us to discriminate between uninjured/slightly injured animals and animals that developed severe lesions. Decisional statistics showed that several glycan families were down-regulated whereas others increased, and that particular structures were statistically significantly changed in the serum of locally irradiated mice. The observed increases in multiantennary N-glycans and in outer branch fucosylation and sialylation were associated with the up-regulation of genes involved in glycosylation in the liver, which is the main producer of serum proteins, and with an increase in the key proinflammatory serum cytokines IL-1β, IL-6, and TNFα, which can regulate the expression of glycosylation genes. Our results suggest for the first time a role of serum protein glycosylation in response to irradiation. These protein-associated glycan structure changes might signal radiation exposure or effects.
authors.affiliation: Institut de Radioprotection et de Sûreté Nucléaire (IRSN), DRPH, SRBE, LRTE, 92260 Fontenay-aux-Roses, France.
authors.forename: Thibault
authors.initials: T
authors.lastname: Chaze
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Slomianny
authors.forename: Fabien
authors.initials: F
authors.lastname: Milliat
authors.forename: Georges
authors.initials: G
authors.lastname: Tarlet
authors.forename: Tony
authors.initials: T
authors.lastname: Lefebvre-Darroman
authors.forename: Patrick
authors.initials: P
authors.lastname: Gourmelon
authors.forename: Eric
authors.initials: E
authors.lastname: Bey
authors.forename: Marc
authors.initials: M
authors.lastname: Benderitter
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Michalski
authors.forename: Olivier
authors.initials: O
authors.lastname: Guipaud
mesh_terms: D000328:Adult; D000818:Animals; D001798:Blood Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002056:Burns / Q000097:blood* / Q000209:etiology / Q000235:genetics; D002240:Carbohydrate Sequence; D015180:Electrophoresis, Gel, Two-Dimensional; D005720:Gamma Rays / Q000009:adverse effects; D005786:Gene Expression Regulation; D054794:Glycomics; D006031:Glycosylation; D006801:Humans; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000378:metabolism / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000097:blood* / Q000737:chemistry; D025341:Principal Component Analysis; D011499:Protein Processing, Post-Translational; D011833:Radiation Injuries, Experimental / Q000097:blood* / Q000209:etiology / Q000235:genetics; D012867:Skin / Q000378:metabolism / Q000528:radiation effects*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D001798:Blood Proteins; D053583:Interleukin-1beta; D015850:Interleukin-6; D011134:Polysaccharides; D014409:Tumor Necrosis Factor-alpha