Organophosphorous and organochlorine pesticides affect human placental phosphoinositides metabolism and PI-4 kinase activity

• Published in: Journal of biochemical and molecular toxicology 2004, Vol.18 (1), p.30-36
• Main Authors: Souza, María S., de Potas, Gladis Magnarelli, de D'Angelo, Ana M. Pechén
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 4-Kinase - metabolism; Azinphosmethyl - toxicity; Cells, Cultured; Chlorpyrifos - toxicity; DDT - toxicity; Female; Heptachlor - toxicity; Human Placenta; Humans; Insecticides - toxicity; Organochlorine Pesticides; Organophosphorous Pesticides; Phosphatidylinositols - metabolism; Phosphoinositides; Phosphorylation - drug effects; PI 4-Kinase; Placenta - cytology; Placenta - drug effects; Placenta - metabolism; Pregnancy
• ISSN: 1095-6670; 1099-0461
• DOI: 10.1002/jbt.20003

The objective of this work was to describe the effect of organophosphorous and organochlorine pesticides on phosphoinositides metabolism in human placenta. Pesticides concentration (10 μM) was used for in vitro incubations of cell‐free homogenates labelled with 32P orthophosphate. Heptachlor (HC) and dichloro‐diphenyl‐trichloroethane (o‐p′ DDT) increased phosphatidyl‐inositol, phosphatidylinositolphosphate, and phosphatidyl‐inositolbiphosphate phosphorylation while azinphosmethyl (AM) increased phosphatidylinositolbiphosphate labeling. Decreased 32P incorporation in phosphatidylinositol was found with phosmet (PM), AM, and chlorpyriphos (CHL). The effects of these xenobiotics on PI4‐kinase activity using different subcellular fractions were also examined. Both type of pesticides affected the postmembrane supernatant enzyme activity. A biphasic effect on membrane and nuclear PI4‐kinase activity was seen with HC. The strongest effect found was seen with o‐p′ DDT in nuclear kinase activity while substantial changes were also observed in membrane. These data demonstrate the sensitivity of human placental PI4‐kinase to pesticides currently found in human tissues and suggest deleterious consequences in different processes regulated by 4‐phosphoinositides. © 2004 Wiley Periodicals, Inc. J Biochem Mol Toxicol 18:30–36, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20003