Heptachlor and o-p'DDT effects on protein kinase activities associated with human placenta particulate fractions.
Organochlorine pesticides have been detected in placenta. The ability of heptachlor (HC) and 1,1,1-tricholoro-2-(2-chlorophenyl)-2-4-chlorophenyl)ethane (o-p'DDT) to interfere with protein phosphorylation was evaluated. In vitro incubations of cell-free placental villi homogenates with a concentration range 1-100 microM were performed. In particulate fractions, total serine/threonine kinase activity was increased by 10 microM HC and o-p' DDT (59% and 82%, respectively). Maximum eightfold increase was observed with 10 microM o-p' DDT on protein kinase A activity. By contrast, protein kinase C activity was reduced by 10 microM HC and o-p' DDT (40% and 52%, respectively). Endogenous substrate phosphorylation studies demonstrated that slight but significant increase in 24-kDa band labeling was produced in nuclear samples with 1, 10, and 100 microM HC and 100 microM o-p' DDT. Exposition to 100 microM HC increased 85-kDa band labeling. In mitochondrial fractions, 10 microM HC and o-p' DDT increased 24- and 65-kDa bands' labeling. These data indicate that both pesticides affect protein kinase activities in particulate fraction. Nuclear compartmentalization of these compounds, insertion in membranes, and chemical stress production may be associated to the observed effects, thus suggesting deleterious consequences in signaling pathways.
Magnarelli
Gladis
G
LIBIQUIMA, Chemistry Department, Universidad Nacional del Comahue, Buenos Aires 1400, Neuquén, Argentina. ggmagnarelli@yahoo.com.ar
Souza
María S
MS
de D'Angelo
Ana M Pechén
AM
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D002467:Cell Nucleus / Q000201:enzymology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D003634:DDT / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006533:Heptachlor / Q000494:pharmacology*; D006801:Humans; D007306:Insecticides / Q000494:pharmacology*; D008928:Mitochondria / Q000201:enzymology*; D010766:Phosphorylation; D010920:Placenta / Q000166:cytology / Q000201:enzymology*; D011247:Pregnancy; D011493:Protein Kinase C / Q000378:metabolism*
D007306:Insecticides; D006533:Heptachlor; D003634:DDT; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C