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 language | English |
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Pages (from-to) | 1634-9 |
Number of pages | 6 |
Journal | Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society |
Volume | 12 |
Issue number | 11 |
DOIs | |
Publication status | Published - 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