Quick study: Death probes
THE QUESTION: Can research tools be devised to better define the sequence of events that occurs during apoptosis, or programmed cell death?
THE BACKGROUND: If a cell is damaged beyond repair or has outlived its usefulness, it needs to die, which the body accomplishes by triggering apoptosis in the cell. But apoptosis can also be triggered inappropriately, often after a trauma to the body, causing healthy cells to die. If researchers uncover the intracellular sequence of steps that culminates in cell death, it could lead to better ways to control it.
When apoptosis is triggered, a series of enzymes called caspases are activated that ultimately orchestrate the destruction of the cell. While much is known about the primary apoptosis activation pathways in single cells, less is known about how these pathways function in the context of whole tissues and organs. Furthermore, many of the transient intermediate forms of active caspases that are produced when the cell death signal is activated are not well understood because of a lack of tools to identify them.
THE STUDY: Activated caspases normally bind to protein substrates, which they then cleave into pieces. The researchers built small molecule probes containing different bits of protein sequences linked to a chemically reactive agent. The idea was to trick the caspases into latching onto the probes. The probes were mixed with either proteins from cells or intact live cells and apoptosis was artificially triggered. The reactive agents allowed the researchers to measure which caspases were activated and when.
RESULTS: The probes are promising tools to study apoptosis. They allowed researchers to see what was happening at different stages of apoptosis and to start mapping the process. Their analyses also identified previously unknown intermediate forms of caspases.
WHY IT MATTERS: Using these molecular probes, which will be made available to any scientist who wants them, researchers can continue unraveling the secrets of the process of cell death. That could open the door to devising ways to monitor the effectiveness of various chemotherapies that trigger apoptosis in cancer cells. It also could lead to new interventions against the inappropriate apoptosis that happens after heart attacks and strokes.
STANFORD CONNECTION: The study was conducted by Alicia Berger, graduate student in cancer biology working in the lab of Matthew Bogyo, PhD, assistant professor of pathology and of microbiology and immunology and, by courtesy, of molecular pharmacology.
FIND THIS STUDY: Published in the Aug. 18 issue of Molecular Cell. Available online at http://www.molecule.org.