The Endocrine-Disrupting Compound, Nonylphenol, Inhibits Neurotrophin-Dependent Neurite Outgrowth
| Autor: | Elena Y. Bryleva, Hongbin Liu, Donna M. Porter, Tyler J. Hendershot, Cassandra L. Bevan, Leslie P. Henderson, Marthe J. Howard, Christopher R. Schumann |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
medicine.medical_specialty
Neurite Cell Survival Xenopus Tropomyosin receptor kinase A Pertussis toxin PC12 Cells Phosphatidylinositol 3-Kinases Xenopus laevis chemistry.chemical_compound Endocrinology Phenols Endocrine disrupting compound GTP-Binding Proteins Internal medicine Nerve Growth Factor Neurites medicine Animals Phosphatidylinositol Cells Cultured Estradiol biology Glycogen Synthase Kinases Cell Differentiation biology.organism_classification Cyclic AMP-Dependent Protein Kinases Rats Nerve growth factor Pertussis Toxin Receptors Estrogen Spinal Cord chemistry biology.protein Mitogen-Activated Protein Kinases Proto-Oncogene Proteins c-akt Signal Transduction Neurotrophin |
| Zdroj: | Endocrinology. 147:4192-4204 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2006-0581 |
| Popis: | Endocrine-disrupting compounds (EDCs) may interfere with neuronal development due to high levels of accumulation in biological tissue and potentially aberrant steroid signaling. Treatment of dissociated embryonic Xenopus spinal cord neurons with the EDC, nonylphenol (NP), did not alter cell survival or neurite outgrowth but inhibited neurotrophin-induced neurite outgrowth, effects that were recapitulated by treatment with comparable concentrations of 17 beta-estradiol (E2) and beta-estradiol 6-(O-carboxy-methyl)oxime: BSA (E2-BSA), but not a synthetic androgen. Effects of NP were not inhibited by the nuclear estrogen receptor antagonist, ICI 182,780, but were inhibited by the G protein antagonist, pertussis toxin. Nerve growth factor (NGF)-induced neurite outgrowth in Xenopus neurons was shown to require MAPK signaling. NP did not affect TrkA expression, MAPK signaling, or phosphatidylinositol 3' kinase-Akt-glycogen synthase kinase 3 beta (PI3K-Akt-GSK3 beta) signaling in Xenopus. The ability of NP to inhibit NGF-induced neurite outgrowth without altering survival was recapitulated in the rat pheochromocytoma (PC12) cell line. As with Xenopus neurons, the inhibitory actions of NP in PC12 cells were not antagonized by ICI 182,780 and did not involve alterations in signaling along either the MAPK or PI3K-Akt-GSK3 beta pathways. NP did significantly inhibit the ability of NGF to increase protein kinase A activity in this cell line. These data have important implications with respect to potentially deleterious effects of NP exposure during early neural development and highlight the fact that bioaccumulation of EDCs, such as NP, may elicit very disparate effects along divergent signaling pathways than those that arise from the actions of physiological levels of endogenous estrogens. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|