Large-Scale Quantitative Proteomic Approach to Identifying Sulfur Mustard-Induced Protein Phosphorylation Cascades

摘要

The use of sulfur mustard SM, bis-(2-chloroethyl) sulfide as a chemical warfare agent dates back to World War I. Unfortunately, there is no current treatment, and relatively little is known about which proteins play a major role in SM-induced toxicity. Indeed, a milieu of signaling molecules respond to SM, triggering many pathways including apoptosis, inflammation, and DNA damage (1). Recent reports have shown that SM exposure activates specific proteins, such as p53, NF-kappaB, Bcl- 2, and others (1). While these studies are effective at probing individual pathways, they do not put into context the global changes that are occurring in response to SM and how these many signaling pathways intersect; thus, they provide only a limited snapshot of SM- induced toxicity. Over the past few years, innovations in systems biology and biotechnology have led to important advances in our understanding of biological phenomena. This is due in part to better instrumentation and software development. In particular, the field of proteomics has been accelerated by more accurate and high-throughput mass spectrometry instrumentation. Protein samples that once took hours to evaluate can now be analyzed in a matter of seconds. Technologies that allow for rapid, sensitive, and specific analysis of the cellular proteome have already proven effective at answering a range of biological questions, from targeted studies to global analyses.