Organophosphorus compounds alter intracellular F-actin content in SH-SY5Y human neuroblastoma cells

Cytoskeletal components, especially, f-actin (filamentous actin), are responsible for neurite extension and maintenance. Alterations in neurite length and quality precede in vitro cell death induced by organophosphorus (OP) compounds and implicate f-actin proteins in this process. We, therefore, investigated changes in f-actin in SH-SY5Y human neuroblastoma cells exposed to 0.1 and 1 mM paraoxon, parathion, phenyl saligenin phosphate (PSP), triortho-tolyl phosphate (TOTP), triphenylphosphite (TPPi), and di-isopropyl phosphorofluoridate (DFP)for 0-48 h. The f-actin was measured by flow cytometry, in cells labeled with Alexa 488 phalloidin. The relative amount off-actin was compared to total protein levels as determined by, spectrophotometry. The cellular content of f-actin significantly decreased following exposure to PSP (0.1 mM, >30 min; 1 mM, > 15 min), TOTP (0.1 mM, 16 h; 1 mM, > 15 min), TPPi (1 mM, >4 h), paraoxon (1 mM, >24 h), and parathion (1 mM, 48 h). Exposure to DFP (0.1 and I mM) did not significantly alter f-actin content at any, time point. Exposure to parathion (0.1 W 48 h) significantly increased the amount of cellular f-actin. Total protein was significantly decreased after exposure to PSP (0.1 and 1 mM, >8 h) and TPPi (1 mM, 48 h). Significant increases in total protein were observed following exposure to parathion (0.1 mM, >3 h). Consistent alterations in the protein content of DFP-exposed samples were not observed. These results suggest that the loss off-actin is an early, event following OP compound exposure and that this loss significantly precedes a loss of protein content for some OP compounds (PSP, TPPi). Results also imply that under other exposure conditions (TOTP, paraoxon, parathion) alterations in the f-actin content are independent of protein content. (C) 2001 Elsevier Science Inc. All rights reserved.