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Isoform-specific alanine aminotransferase measurement candistinguish hepatic from extrahepatic injury in humans
Safety Assessment, AstraZeneca, Södertälje.
Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Surgery, Karolinska Institute at Karolinska University Hospital.
Department of Medicine, University of Helsinki, Helsinki, Finland.
Department of Clinical Science, Intervention and Technology (CLINTEC), Division of Surgery, Karolinska Institute at Karolinska University Hospital.
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2012 (English)In: International Journal of Molecular Medicine, ISSN 1107-3756, E-ISSN 1791-244X, Vol. 30, 1241-1249 p.Article in journal (Refereed) Published
Abstract [en]

Serum alanine aminotransferase (ALT) is used asa clinical marker to detect hepatic damage and hepatoxicity.Two isoforms of ALT have been identified, ALT1 and ALT2,which have identical enzymatic capacities and are detectedsimultaneously in human serum/plasma using classical clinicalchemical assays. Differences exist in the expression patterns ofthe ALT1 and ALT2 proteins in different organs which suggestthat changes in the proportion of ALT1 and ALT2 in plasmamay arise and reflect damage to different human organs.However, this has not been previously studied due to the lackof a selective methodology that can quantify both ALT1 andALT2 isoforms in the total ALT activity normally measuredin clinical samples. To the best of our knowledge, our currentstudy reveals for the first time, that under 3 different conditionsof liver damage (non-alcoholic fatty liver disease, hepatitis Cand during liver surgery) the leakage of ALT1 activity intoplasma greatly exceeds that of ALT2, and that the measurementof ALT1 during liver damage is equal to the measurement oftotal ALT activity. By contrast, during skeletal muscle injury,induced in volunteers by physical exertion, the leakage ofALT2 exceeds that of ALT1 and the proportion of circulatingALT isoforms changes accordingly. The ALT isoform changesoccurring in plasma reflect previously demonstrated relativecontents of ALT1 and ALT2 activities in human liver and skeletalmuscle. These data suggest that assessing the percentagecontribution of ALT1 and ALT2 activities to total ALT activityin plasma may distinguish hepatic from extrahepatic injuryusing the same standard analytical platform.

Place, publisher, year, edition, pages
2012. Vol. 30, 1241-1249 p.
Keyword [en]
alanine aminotransferase, liver injury, biomarkers, skeletal muscle injury, creatine kinase
National Category
Clinical Medicine
Research subject
Medicine/Technology
Identifiers
URN: urn:nbn:se:gih:diva-2381DOI: 10.3892/ijmm.2012.1106PubMedID: 22922605OAI: oai:DiVA.org:gih-2381DiVA: diva2:544430
Available from: 2012-08-14 Created: 2012-08-14 Last updated: 2017-03-31Bibliographically approved

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Mattsson, C. MikaelEkblom, Björn
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