Figure 1. Digeranyl bisphosphonate attenuates Rac1 activity and H₂O₂ production.

(A) Schematic flow diagram of isoprenoid pathway. (B) Chemical diagram of digeranyl bisphophonate (DGBP). U.S. Patent: 7,268,164. (C) Schematic flow diagragm of the isopresnoid pathway showing the location of DGBP inhibition of GGPP synthase. (D) Macrophages were cultured overnight with vehicle (water) or DGBP (10 μM). Cells were exposed to chrysotile (10 μg/cm²) for 30 min. Cells were fractionated into aqueous or detergent phases. Lysates were subjected to immunoblot analysis for Rap 1A and Rac1. (E) Macrophages were cultured overnight with vehicle or DGBP (10 μM) and exposed to chrysotile (10 μg/cm²) for 30 min. Immunoblot analysis was performed for Rap 1A and Rac1 in isolated mitochondria (upper panel) and cytoplasm (lower panel). (F) Macrophages were cultured overnight with vehicle or DGBP (10 μM) and exposed to chrysotile (10 μg/cm² for 30 min. Rac1 activity was measured by G-LISA and normalized to protein concentration. n = 4, * p < 0.018 vs. - chrysotile (vehicle) and ** p < 0.022 vs. chrysotile (vehicle). (G) Macrophages were cultured in the presence vehicle or DGBP (10 μM) overnight and exposed to chrysotile (10 μg/cm²) for 30 min. H₂O₂ was measured by pHPA assay and is expressed in pmoles/mg. n = 5, * p < 0.0001 vs. all other conditions.