BioProject

Azaspiracid-1 (AZA-1) is a marine phycotoxin that accumulates in shellfish and known to cause severe gastrointestinal intoxications in humans. More...

Azaspiracid-1 (AZA-1) is a marine phycotoxin that accumulates in shellfish and known to cause severe gastrointestinal intoxications in humans. As the mechanism of action of AZA-1 is currently unknown, human DNA microarrays were used to profile gene expression in human lymphocyte T cells following AZA-1 exposure. Highly significant early (1 hr) genes consisted of a T cell specific transcription factor, membrane proteins, receptors, and inflammatory genes. At 4 hr, responding genes included transcription factors and cell growth genes, in addition to 16 genes involved in fatty acid and cholesterol synthesis. Similarly, at 24 hr, 17 of the top 35 signature genes were involved in fatty acid and cholesterol synthesis. Gene Map Annotator and Pathway Profiler software confirmed cell signaling effects targeted toward lipid biosynthesis pathways. The transcriptional profile induced by AZA-1 shared high similarity to expression profiles of in vitro cholesterol synthesis inhibitor studies and in vitro and in vivo cholesterol synthesis gene knockout studies, suggesting a common transcriptional response and possible mechanism of action. Keywords: Time course; AZA treatment vs. vehicle control Overall design: Time course experiment comparing AZA treatment gene expression to vehicle control. Parallel cultures of cells (n=2) were exposed to AZA or vehicle control for 1, 4, 24hr and harvested for RNA extraction. dye swaps were used for the replicate time points. Log Ratio data are listed as Log10. Less...