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In Vivo Monitoring of Liver Damage Using Caspase-3 Probe

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Title: In Vivo Monitoring of Liver Damage Using Caspase-3 Probe
Authors: Ozaki, Michitaka Browse this author →KAKEN DB
Haga, Sanae Browse this author
Ozawa, Takeaki Browse this author
Keywords: imaging
non-invasive monitoring
optical probe
Issue Date: Feb-2012
Publisher: Ivyspring International Publisher
Journal Title: Theranostics
Volume: 2
Issue: 2
Start Page: 207
End Page: 214
Publisher DOI: 10.7150/thno.3806
Abstract: Real-time monitoring of cellular and organ conditions improves our understanding of various physiopathological phenomena. Such monitoring is expected to provide important alternatives for clinical diagnosis and therapy. We have sought to show physiopathological changes of organs as well as cells. Here, we present an example of in vivo imaging of liver states using the luciferase-based caspase-3 optical probe. We examined dynamic changes of apoptosis (caspase-3 activity) of a mouse liver as well as those of liver cells, proving that the emitted signals reflected the biochemically evaluated apoptotic cell death. In live liver cell (AML 12) experiments, the optical probe for caspase-3 activity emitted signals in response to Fas-ligand, staurosporine and hypoxia/reoxygenation, demonstrating that the probe can measure cellular apoptosis quantitatively. We therefore applied this probe for mouse liver ischemia/reperfusion (I/R) and drug-toxicity to liver. By expressing the probe in a mouse liver adenovirally, we imaged liver caspase-3 activity (i.e. apoptotic damage) non-invasively and chronologically in the hepatic I/R model of mice. The duration of liver ischemia affected the post-ischemic caspase-dependent damage. Ischemia (up to 60 min) enhanced liver damage after reperfusion, but prolonged ischemia (90 min of ischemia) induced not apoptotic cell death but necrotic cell death. Direct observations of the changes of organ conditions elucidated the dynamism of organ function and damage. These technologies clearly possess clinical relevance. They are expected to provide a new diagnostic tool for various clinical settings in the future.
Rights: © 2012 Ivyspring International Publisher
Type: article
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 尾崎 倫孝

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