Document Detail


Glycocapture-assisted global quantitative proteomics (gagQP) reveals multiorgan responses in serum toxicoproteome.
MedLine Citation:
PMID:  23540550     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Bingyun Sun; Angelita G Utleg; Zhiyuan Hu; Shizhen Qin; Andrew Keller; Cynthia Lorang; Li Gray; Amy Brightman; Denis Lee; Vinita M Alexander; Jeffrey A Ranish; Robert L Moritz; Leroy Hood
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2013-04-11
Journal Detail:
Title:  Journal of proteome research     Volume:  12     ISSN:  1535-3907     ISO Abbreviation:  J. Proteome Res.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-05-03     Completed Date:  2013-12-03     Revised Date:  2013-12-17    
Medline Journal Info:
Nlm Unique ID:  101128775     Medline TA:  J Proteome Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2034-44     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Acetaminophen / toxicity*
Alanine Transaminase / metabolism
Analgesics, Non-Narcotic / toxicity*
Animals
Blood Proteins / chemistry,  isolation & purification,  metabolism*
Drug-Induced Liver Injury / blood*
Glycopeptides / chemistry,  isolation & purification
Glycosylation
Humans
Liver / drug effects,  enzymology,  pathology
Male
Mice
Mice, Inbred C57BL
Molecular Sequence Annotation
Organ Specificity
Protein Interaction Maps
Proteome / chemistry,  isolation & purification,  metabolism*
Grant Support
ID/Acronym/Agency:
P50 GM076547/GM/NIGMS NIH HHS; RC2 HG005805/HG/NHGRI NIH HHS
Chemical
Reg. No./Substance:
0/Analgesics, Non-Narcotic; 0/Blood Proteins; 0/Glycopeptides; 0/Proteome; 362O9ITL9D/Acetaminophen; EC 2.6.1.2/Alanine Transaminase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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