Spatiotemporal expression of heme oxygenase-1 detected by in vivo bioluminescence after hepatic ischemia in HO-1/Luc mice

Huawei Su, Gooitzen M van Dam, Carlijn I Buis, Dorien S Visser, Jan Willem Hesselink, Theo A Schuurs, Henri G D Leuvenink, Christopher H. Contag, Robert J Porte

    Research output: Contribution to journalArticleAcademicpeer-review

    Abstract

    Upregulation of heme oxygenase-1 (HO-1) has been proposed as a critical mechanism protecting against cellular stress during liver transplantation, providing a potential target for new therapeutic interventions. We investigated the feasibility of in vivo bioluminescence imaging (BLI) to noninvasively quantify the spatiotemporal expression of HO-1 after warm hepatic ischemia in living animals. Luciferase activity was measured by BLI as an index of HO-1 transcription in transgenic reporter mice (Ho1-luc) at standardized time points after 60 minutes of warm hepatic ischemia. HO-1 mRNA levels were measured in postischemic livers of mice sacrificed at the same time points in separate experiments. Bioluminescent signals from postischemic liver lobes were first detected at 3 hours after reperfusion. Peak levels were reached at 9 hours, after which bioluminescent activity declined and returned to baseline values at 48 hours after reperfusion. Upregulation of HO-1 as detected by in vivo BLI was preceded by increased HO-1 mRNA expression and confirmed by enhanced immunohistochemical staining of hepatocytes. In conclusion, this study shows that in vivo BLI allows a sensitive assessment of HO-1 expression after hepatic ischemia in living animals. The capability of whole-body temporal imaging of HO-1 expression provides a valuable tool in the development of novel strategies to modulate HO-1 expression in liver transplantation.

    Original languageEnglish
    Pages (from-to)1634-9
    Number of pages6
    JournalLiver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
    Volume12
    Issue number11
    DOIs
    Publication statusPublished - Nov 2006

    Keywords

    • Animals
    • Feasibility Studies
    • Heme Oxygenase-1
    • Immunohistochemistry
    • Ischemia
    • Liver
    • Luciferases
    • Luminescent Measurements
    • Male
    • Mice
    • Mice, Transgenic
    • RNA, Messenger
    • Reperfusion Injury
    • Staining and Labeling
    • Time Factors
    • Tissue Distribution
    • Warm Ischemia
    • Journal Article
    • Research Support, Non-U.S. Gov't

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