The Water Channel Aquaporin 1 Is a Novel Molecular Target of Polychlorinated Biphenyls for in Utero Anomalies
| Autor: | David W Murray, Satyan Kalkunte, Neetu Tewari, Surendra Sharma |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Spiral artery
medicine.medical_specialty Placenta Intrauterine growth restriction Cell Communication Biology Biochemistry Cell Line Mice Molecular Basis of Cell and Developmental Biology Pregnancy In vivo Internal medicine medicine Animals Humans Antibodies Blocking Molecular Biology Aquaporin 1 Endothelial Cells Interleukin Biological Transport Arteries Cell Biology Chlorodiphenyl (54% Chlorine) medicine.disease Interleukin-10 Trophoblasts Mice Inbred C57BL Pregnancy Trimester First Interleukin 10 Endocrinology medicine.anatomical_structure In utero Prenatal Exposure Delayed Effects Premature Birth Female Nervous System Diseases |
| Zdroj: | Journal of Biological Chemistry. 284:15224-15232 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m808892200 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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