Review
Cell Research (2008) 18:238–247. doi: 10.1038/cr.2008.17; published online 29 January 2008
Intracellular protease activation in apoptosis and cell-mediated cytotoxicity characterized by cell-permeable fluorogenic protease substrates
Beverly Z Packard1 and Akira Komoriya1
1OncoImmunin Inc5., 207A Perry Parkway, Suite 6, Gaithersburg, MD 20877, USA
Correspondence: Beverly Z Packard, Tel: +1-301-987-7881; Fax: +1-301-987-7882 E-mail: BPackard@PhiPhiLux.com
Abstract
Over the past decade the importance of signaling from reporter molecules inside live cells and tissues has been clearly established. Biochemical events related to inflammation, tumor metastasis and proliferation, and viral infectivity and replication are examples of processes being further defined as more molecular tools for live cell measurements become available. Moreover, in addition to quantitating parameters related to physiologic processes, real-time imaging of molecular interactions that compose basic cellular activities are providing insights into understanding disease mechanisms as well as extending clinical efficacy of therapeutic regimens. In this review the use of highly cell-permeable fluorogenic substrates that report protease activities inside live cells is described; applications to defining the molecular events of two cellular processes, i.e., apoptosis and cell-mediated cytotoxicity, are then illustrated.
Keywords:
protease, substrate, fluorescence, caspase, granzyme, apoptosis, cytotoxicity
Abbreviations:
(ADCC), antibody-dependent cellular cytotoxicity; (CTL), CD8+ cytotoxic T lymphocyte; (DIC), differential interference contrast; (GzB), Granzyme B; (MAb), monoclonal antibody; (NK cell), natural killer cell; (PI), propidium iodide; (PTD), protein transduction domain
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