Quantitative liver-specific protein fingerprint in blood: A signature for hepatotoxicity

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dc.contributor.authorHu, Z.en_US
dc.contributor.authorLausted, C.en_US
dc.contributor.authorYoo, Hyuntaeen_US
dc.contributor.authorYan, X.en_US
dc.contributor.authorBrightman, A.en_US
dc.contributor.authorChen, J.en_US
dc.contributor.authorWang, W.en_US
dc.contributor.authorBu, X.en_US
dc.contributor.authorHood, L.en_US
dc.date.accessioned2014-07-18T17:15:01Z
dc.date.available2014-07-18T17:15:01Z
dc.date.created2014-01-14
dc.date.issued2014-01-14en_US
dc.date.submitted2013-10-11en_US
dc.description.abstractWe discuss here a new approach to detecting hepatotoxicity by employing concentration changes of liver-specific blood proteins during disease progression. These proteins are capable of assessing the behaviors of their cognate liver biological networks for toxicity or disease perturbations. Blood biomarkers are highly desirable diagnostics as blood is easily accessible and baths virtually all organs. Fifteen liver-specific blood proteins were identified as markers of acetaminophen (APAP)-induced hepatotoxicity using three proteomic technologies: label-free antibody microarrays, quantitative immunoblotting, and targeted iTRAQ mass spectrometry. Liver-specific blood proteins produced a toxicity signature of eleven elevated and four attenuated blood protein levels. These blood protein perturbations begin to provide a systems view of key mechanistic features of APAP-induced liver injury relating to glutathione and S-adenosyl-L-methionine (SAMe) depletion, mitochondrial dysfunction, and liver responses to the stress. Two markers, elevated membrane- bound catechol-O-methyltransferase (MB-COMT) and attenuated retinol binding protein 4 (RBP4), report hepatic injury significantly earlier than the current gold standard liver biomarker, alanine transaminase (ALT). These biomarkers were perturbed prior to onset of irreversible liver injury. Ideal markers should be applicable for both rodent model studies and human clinical trials. Five of these mouse liver-specific blood markers had human orthologs that were also found to be responsive to human hepatotoxicity. This panel of liver-specific proteins has the potential to effectively identify the early toxicity onset, the nature and extent of liver injury and report on some of the APAP-perturbed liver networks.en_US
dc.identifier.bibliographicCitationHu, Z., C. Lausted, H. Yoo, X. Yan, et al. 2014. "Quantitative liver-specific protein fingerprint in blood: A signature for hepatotoxicity." Theranostics 4(2): 215-228.en_US
dc.identifier.issn1838-7640en_US
dc.identifier.issue2en_US
dc.identifier.startpage215en_US
dc.identifier.urihttp://hdl.handle.net/10735.1/3731
dc.identifier.volume4en_US
dc.language.isoenen_US
dc.relation.urihttp://dx.doi.org/10.7150/thno.7868
dc.rightsCC BY-NC-ND 3.0 (Attribution-NonCommercial-NoDerivatives)en_US
dc.rights©2014 Ivyspring International Publisher.en_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/en_US
dc.sourceTheranostics
dc.subjectLiver--Wounds and injuriesen_US
dc.subjectBHMT proteinen_US
dc.subjectBiological Markersen_US
dc.subjectCOMT proteinen_US
dc.subjectRBP4 proteinen_US
dc.titleQuantitative liver-specific protein fingerprint in blood: A signature for hepatotoxicityen_US
dc.typeTexten_US
dc.type.genreArticleen_US

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Yoo, Hyuntae
CSB Research