They were right. In the new report, the team shows that the luciferase-DEVD-ER complex released much less light than luciferase alone in either cell cultures or in mice with cancer that had been injected with a DNA sequence encoding the complex. When they added another ER and DEVD to the other side of the luciferase, the amount of light emitted was cut even further.
But when the researchers added an experimental cancer-fighting drug called TRAIL, which is known to cause apoptosis, it was just like turning on a light switch.
As the drug caused the activation of the caspase-3 enzyme, the bonds between the luciferase and its light-hiding companion ER molecules were cut at the DEVD cleavage site, and the light-emitting process began. One hour after TRAIL treatment, the amount of light emitted from the mice had gone up by 186 percent. Mice that received a placebo instead of TRAIL emitted only about 21 percent more light than they had before.
Even though only a few photons, or particles of light, can escape a mouse body from the glowing luciferase, the researchers were able to detect them with a bioluminescence imaging camera that can detect single photons.
The camera, which is kept in a light-proof chamber at ultra-cold temperatures to keep out all stray energy, produced vivid images showing the intensity of light -- and therefore the rate of cell death -- in different regions of the cell cultures or mouse cancer tumors. Rehemtullah notes that the technology is sensitive enough to pick up cell death in areas as small as 100 cells.
"The enzyme was turned on in a protease-dependent manner, and though we used caspase-3 in this instance, we believe it could be any protease that's important to any cellular process," Ross emphasizes. "And, we believe other reporters could be used, including radioactive positro
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Contact: Kara Gavin
umhsmedia@umich.edu
734-764-2220
University of Michigan Health System
17-Dec-2002