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PMID: 12475931 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Noninvasive real-time imaging of apoptosis.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 99 ·No. 26 ·2002-12-24 ·Pages 16551-5

Laxman B, Hall DE, Bhojani MS, Hamstra DA, Chenevert TL, Ross BD, Rehemtulla A

Abstract

Strict coordination of proliferation and programmed cell death (apoptosis) is essential for normal physiology. An imbalance in these two opposing processes results in various diseases including AIDS, neurodegenerative disorders, myelodysplastic syndromes, ischemiareperfusion injury, cancer, autoimmune disease, among others. Objective and quantitative noninvasive imaging of apoptosis would be a significant advance for rapid and dynamic screening as well as validation of experimental therapeutic agents. Here, we report the development of a recombinant luciferase reporter molecule that when expressed in mammalian cells has attenuated levels of reporter activity. In cells undergoing apoptosis, a caspase-3-specific cleavage of the recombinant product occurs, resulting in the restoration of luciferase activity that can be detected in living animals with bioluminescence imaging. The ability to image apoptosis noninvasively and dynamically over time provides an opportunity for high-throughput screening of proapoptotic and antiapoptotic compounds and for target validation in vivo in both cell lines and transgenic animals.

MeSH Terms
Animals Apoptosis/drug effects Apoptosis Regulatory Proteins Caspase 3 Caspases/metabolism Enzyme Activation Glioma/drug therapy,pathology Humans Luciferases/genetics,metabolism Luminescent Measurements Membrane Glycoproteins/therapeutic use Mice Receptors, Estrogen/chemistry,physiology TNF-Related Apoptosis-Inducing Ligand Tumor Cells, Cultured Tumor Necrosis Factor-alpha/therapeutic use
Chemicals
Apoptosis Regulatory Proteins Membrane Glycoproteins Receptors, Estrogen TNF-Related Apoptosis-Inducing Ligand TNFSF10 protein, human Tnfsf10 protein, mouse Tumor Necrosis Factor-alpha Luciferases CASP3 protein, human Casp3 protein, mouse Caspase 3 Caspases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Laxman Bharathi
Center for Molecular Imaging, University of Michigan Medical School, 1150 West Medical Center Drive, Medical Sciences Research Building III, Room 9303, Ann Arbor, MI 48109-0648, USA.
Hall Daniel E
Bhojani Mahaveer Swaroop
Hamstra Daniel A
Chenevert Thomas L
Ross Brian D
Rehemtulla Alnawaz
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.252644499
Published
2002-12-24
Epub
2002-00-10
Pages
16551-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC139181
Subset
IM
Grants
NCI NIH HHS · R24CA83099 · United States
NCI NIH HHS · 1R43CA91448-01 · United States
NCI NIH HHS · 5P20CA86442 · United States
NCI NIH HHS · 1P50CA93990 · United States
NCI NIH HHS · R43 CA091448 · United States
NCI NIH HHS · R24 CA083099 · United States
NCI NIH HHS · P50 CA093990 · United States
External Links
PubMed source DOI: 10.1073/pnas.252644499 PMC Full Text View journal details
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