Spatiotemporal expression of heme oxygenase-1 detected by in vivo bioluminescence after hepatic ischemia in HO-1/Luc mice.
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.
Su
Huawei
H
Surgical Research Laboratory, Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands.
van Dam
Gooitzen M
GM
Buis
Carlijn I
CI
Visser
Dorien S
DS
Hesselink
Jan Willem
JW
Schuurs
Theo A
TA
Leuvenink
Henri G D
HG
Contag
Christopher H
CH
Porte
Robert J
RJ
D000818:Animals; D005240:Feasibility Studies; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D007511:Ischemia / Q000201:enzymology*; D008099:Liver / Q000098:blood supply* / Q000201:enzymology*; D008156:Luciferases / Q000235:genetics; D008163:Luminescent Measurements; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000378:metabolism; D015427:Reperfusion Injury / Q000201:enzymology; D013194:Staining and Labeling; D013997:Time Factors; D014018:Tissue Distribution; D052096:Warm Ischemia
D012333:RNA, Messenger; D008156:Luciferases; D051547:Heme Oxygenase-1