The water channel aquaporin 1 is a novel molecular target of polychlorinated biphenyls for in utero anomalies.
J Biol Chem
; 284(22): 15224-32, 2009 May 29.
Article
em En
| MEDLINE
| ID: mdl-19332547
ABSTRACT
Despite serious health risks in humans and wild life, the underlying mechanisms that explain the gene-environment effects of chemical toxicants are largely unknown. Polychlorinated biphenyls (PCBs) are one of the most ubiquitous environmental toxicants worldwide, with reported epidemiological evidence for reproductive and neurocognitive anomalies in humans. Here, we show that Aroclor 1254, a mixture of structurally distinct PCBs, causes preterm birth in interleukin (IL)-10(-/-) mice at a dose that does not show any adverse effects in wild type mice, highlighting the significance of IL-10 as an anti-toxicant cytokine. Aroclor 1254-treated IL-10(-/-) mice demonstrated increased amniotic fluid, intrauterine growth restriction, and reduced litter size with postnatal neuromotor defects. Further, our results identify aquaporin 1 (AQP1), a potent effector of fluid volume regulation and angiogenic activity, as a novel placental target of PCBs. In vivo or in vitro exposure to Aroclor 1254 coupled with IL-10 deficiency significantly reduced the protein content of AQP1. Reduced uterine AQP1 levels were associated with defective spiral artery transformation. Importantly, recombinant IL-10 reversed PCB-induced in vivo and in vitro effects. These data demonstrate for the first time that the IL-10-AQP1 axis is a novel regulator of PCB-induced in utero effects.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Efeitos Tardios da Exposição Pré-Natal
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Aquaporina 1
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
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Pregnancy
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos
País de publicação:
EEUU
/
ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
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USA