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

Souza, María Sol; Potas, Gladis Magnarelli de; D’Angelo, Alessandra

doi:10.1002/jbt.20003

Cited by 14 publications

(14 citation statements)

References 36 publications

(29 reference statements)

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“…In accordance with these results, in vitro studies also demonstrated that different OCs (endosulfan, DDE, and dieldrin) can rapidly activate ERKs in the pituitary tumor cell line GH 3 /B6/F10, with distinctly different activation patterns [29]. Also, we have demonstrated that human placenta presents differential effects of 10 μM HC and o-p DDT on nuclear PI-4 kinase activity [30].…”

Section: Discussionsupporting

confidence: 68%

Heptachlor and o‐p′DDT effects on protein kinase activities associated with human placenta particulate fractions

Magnarelli

Souza

D’Angelo

2009

J Biochem & Molecular Tox

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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.

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Section: Discussionsupporting

confidence: 68%

Heptachlor and o‐p′DDT effects on protein kinase activities associated with human placenta particulate fractions

Magnarelli

Souza

D’Angelo

2009

J Biochem & Molecular Tox

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“…However, both types of pesticides affected the post-membrane supernatant of PI 4-kinase, a key enzyme in PI metabolic pathway. A biphasic effect on membrane and nuclear PI4-kinase activity was seen with heptachlor (OC), with the strongest effect being found with o-p'-DDT on nuclear PI4-kinase activity, while substantial changes were also observed in membrane fractions (Souza et al, 2004).…”

Section: Targetmentioning

confidence: 98%

Placental Toxicology of Pesticides

Magnarelli¹,

Guiñazú²

2012

Recent Advances in Research on the Human Placenta

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“…Abdel-Rahman and colleagues (2002) further concluded that though the placenta presents a barrier of protection against CPF; at high doses, CPF and its metabolites can cross the placenta and enter into the fetus despite extensive maternal hepatic metabolism, as well as, distribute to all fetal tissues and plasma with elimination occurring at a slow rate. In addition, Souza et al (2004) demonstrated that CPF alters the enzymatic activity of placental PI4-kin ase and phosphatidylinositol handling suggesting that CPF may have membrane disrupting properties. Given that exposure to xenobiotics can alter the function and viability of placenta cells, thereby ostensibly, altering the growth and development of the fetus, we examined whether chlorpyrifos and its metabolites are toxic to placental cells.…”

Section: Introductionmentioning

confidence: 99%

Characterization of chlorpyrifos-induced apoptosis in placental cells

Saulsbury¹,

Heyliger²,

Wang³

et al. 2008

Toxicology

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The mechanism by which chlorpyrifos exerts its toxicity in fetal and perinatal animals has yet to be elucidated. Since the placenta is responsible for transport of nutrients and is a major supplier hormones to the fetus, exposure to xenobiotics that alter the function or viability of placenta cells could ostensibly alter the development of the fetus. In this study, JAR cells were used to determine if CPF and the metabolites 3,5,6-trichloro-2-pyridinol (TCP) and chlorpyrifos-oxon (CPO) are toxic to the placenta. Our results indicate that chlorpyrifos (CPF), and its metabolite chlorpyrifos-oxon (CPO) caused a dose-dependent reduction in cellular viability with CPF being more toxic than its metabolites. Chlorpyrifos-induced toxicity was characterized by the loss of mitochondrial potential, the appearance of nuclear condensation and fragmentation, down-regulation of Bcl-2 as well as upregulation of TNFα and FAS mRNA. Pharmacological inhibition of FAS, nicotinic and TNF-α receptors did not attenuate CPF-induced toxicity. Atropine exhibited minimal ability to reverse toxicity. Furthermore, signal transduction inhibitors PD98059, SP600125, LY294002 and U0126 failed to attenuate toxicity; however, SB202190 (inhibitor of p38α and p38β MAPK) sensitized cells to CPF-induced toxicity. Pan-caspase inhibitor Q-VD-OPh produced a slight but significant reversal of CPF-induced toxicity indicating that the major caspase pathways are not integral to CPF-induced toxicity. Taken collectively, these results suggest that chlorpyrifos induces apoptosis in placental cells through pathways not dependent on FAS/TNF signaling, activation of caspases or inhibition of cholinesterase. In addition, our data further indicates that activation of p38 MAPK is integral to the protection cells against CPF-induced injury.

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

Cited by 14 publications

References 36 publications

Heptachlor and o‐p′DDT effects on protein kinase activities associated with human placenta particulate fractions

Heptachlor and o‐p′DDT effects on protein kinase activities associated with human placenta particulate fractions

Placental Toxicology of Pesticides

Characterization of chlorpyrifos-induced apoptosis in placental cells

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