title: Glycocapture-assisted global quantitative proteomics (gagQP) reveals multiorgan responses in serum toxicoproteome.
abstract: Blood is an ideal window for viewing our health and disease status. Because blood circulates throughout the entire body and carries secreted, shed, and excreted signature proteins from every organ and tissue type, it is thus possible to use the blood proteome to achieve a comprehensive assessment of multiple-organ physiology and pathology. To date, the blood proteome has been frequently examined for diseases of individual organs; studies on compound insults impacting multiple organs are, however, elusive. We believe that a characterization of peripheral blood for organ-specific proteins affords a powerful strategy to allow early detection, staging, and monitoring of diseases and their treatments at a whole-body level. In this paper we test this hypothesis by examining a mouse model of acetaminophen (APAP)-induced hepatic and extra-hepatic toxicity. We used a glycocapture-assisted global quantitative proteomics (gagQP) approach to study serum proteins and validated our results using Western blot. We discovered in mouse sera both hepatic and extra-hepatic organ-specific proteins. From our validation, it was determined that selected organ-specific proteins had changed their blood concentration during the course of toxicity development and recovery. Interestingly, the peak responding time of proteins specific to different organs varied in a time-course study. The collected molecular information shed light on a complex, dynamic, yet interweaving, multiorgan-enrolled APAP toxicity. The developed technique as well as the identified protein markers is translational to human studies. We hope our work can broaden the utility of blood proteomics in diagnosis and research of the whole-body response to pathogenic cues.
authors.affiliation: Institute for Systems Biology , 401 N. Terry Ave., Seattle, Washington 98109, USA. bingyun_sun@sfu.ca
authors.forename: Bingyun
authors.initials: B
authors.lastname: Sun
authors.forename: Angelita G
authors.initials: AG
authors.lastname: Utleg
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Hu
authors.forename: Shizhen
authors.initials: S
authors.lastname: Qin
authors.forename: Andrew
authors.initials: A
authors.lastname: Keller
authors.forename: Cynthia
authors.initials: C
authors.lastname: Lorang
authors.forename: Li
authors.initials: L
authors.lastname: Gray
authors.forename: Amy
authors.initials: A
authors.lastname: Brightman
authors.forename: Denis
authors.initials: D
authors.lastname: Lee
authors.forename: Vinita M
authors.initials: VM
authors.lastname: Alexander
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Ranish
authors.forename: Robert L
authors.initials: RL
authors.lastname: Moritz
authors.forename: Leroy
authors.initials: L
authors.lastname: Hood
mesh_terms: D000082:Acetaminophen / Q000633:toxicity*; D000410:Alanine Transaminase / Q000378:metabolism; D018712:Analgesics, Non-Narcotic / Q000633:toxicity*; D000818:Animals; D001798:Blood Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood*; D006020:Glycopeptides / Q000737:chemistry / Q000302:isolation & purification; D006031:Glycosylation; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058977:Molecular Sequence Annotation; D009928:Organ Specificity; D060066:Protein Interaction Maps; D020543:Proteome / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D018712:Analgesics, Non-Narcotic; D001798:Blood Proteins; D006020:Glycopeptides; D020543:Proteome; D000082:Acetaminophen; D000410:Alanine Transaminase
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