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

Abstract
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), tri-ortho-tolyl phosphate (TOTP), triphenyl phosphite (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 decreasedfollowing 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 1 mM) did not significantly alter f-actin content at any time point. Exposure to parathion (0.1 mM, 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.
AuthorsK Carlson, M Ehrich
JournalNeurotoxicology (Neurotoxicology) Vol. 22 Issue 6 Pg. 819-27 (Dec 2001) ISSN: 0161-813X [Print] Netherlands
PMID11829415 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Actins
  • Neoplasm Proteins
  • Organophosphorus Compounds
Topics
  • Actins (metabolism)
  • Brain Neoplasms (metabolism)
  • Cell Adhesion (drug effects)
  • Cell Movement (drug effects)
  • Cytoskeleton (drug effects, metabolism)
  • Flow Cytometry
  • Humans
  • Microscopy, Fluorescence
  • Neoplasm Proteins (metabolism)
  • Neuroblastoma (metabolism)
  • Organophosphorus Compounds (pharmacology)
  • Tumor Cells, Cultured

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