Identification of trichostatin A as a novel transcriptional up-regulator of scavenger receptor BI both in HepG2 and RAW 264.7 cells

Scavenger receptor class B type I (SR-BI) and its human homologue CLA-1 plays an important role in reverse cholesterol transport (RCT). Using a previously established cell-based CLA-1 Up-regulator screening assay, one of the positive strains, 04-9179, presented potent activity in elevating CLA-1 transcriptional level. We report here the identification of an active compound 9179A as a known compound trichostatin A (TSA), and its effects on CLA-1/SR-BI expression both in HepG2 human hepatoma cells and RAW 264.7 murine macrophage cells in vitro. The results showed that the mRNA and Protein level of CLA-1/SR-BI were significantly up-regulated by 9179A both in HepG2 and RAW 264.7 cells. Corresponding to this, the uptake of Dil-HDL by both cells and the efflux of [H-3]cholesterol by RAW 264.7 cells were increased by 9179A in close-dependent manner. ABCA1 was also increased but SR-A decreased by 9179A in RAW 264.7 cells. Using a combination of reporter assays with various deletion in CLA-1 promoter and electrophoretic mobility shift assay, we demonstrated that -419/-232 bp fragment of the CLA-1 promoter mediated (lie effects of 9179A (i.e., TSA). Together, these studies identified TSA as a novel Up-regulator of CLA-1/SR-BI both in HepG2 and RAW 264.7 cells. (C) 2008 Elsevier Ireland Ltd. All rights reserved.