title: Augmented 5-HT Secretion in Pulmonary Neuroepithelial Bodies from PHD1 Null Mice.
abstract: Sustained exposure to low oxygen concentration leads to profound changes in gene expression to restore oxygen homeostasis. Hypoxia-inducible factors (HIFs) comprise a group of transcription factors which accumulate under hypoxia and contribute to the complex changes in gene expression. Under normoxic conditions HIFs are degraded by prolyl-hydroxylases (PHD), however during hypoxia this degradation is inhibited causing HIF accumulation and subsequent changes in gene expression. Pulmonary neuroepithelial bodies (NEB) are innervated serotonin (5-HT)-producing cells distributed throughout the airway epithelium. These putative O(2) sensors are hypothesized to contribute to the ventilatory response to hypoxia. NEB dysfunction has been implicated in several paediatric lung diseases including neuroendocrine cell hyperplasia of infancy and sudden infant death syndrome, both characterized by a marked NEB hyperplasia with unknown functional significance. We have previously reported striking NEB hyperplasia in PHD1(-/-) mice making these mice a potential model to study the role of NEBs in paediatric lung diseases. Here we report in vitro studies on 5-HT release from NEB using this model.
authors: Division of Pathology, Department of Pediatric Laboratory Medicine, The Research Institute, The Hospital for Sick Children and Department of Laboratory Medicine and Pathobiology, University of Toronto, 555 University Avenue, M5G1X8, Toronto, ON, Canada.
authors: Simon
authors: S
authors: Livermore
authors: Jie
authors: J
authors: Pan
authors: Herman
authors: H
authors: Yeger
authors: Peter
authors: P
authors: Ratcliffe
authors: Tammie
authors: T
authors: Bishop
authors: Ernest
authors: E
authors: Cutz
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D008171:Lung Diseases / Q000209:etiology*; D051379:Mice; D018345:Mice, Knockout; D046568:Neuroepithelial Bodies / Q000378:metabolism*; D011393:Procollagen-Proline Dioxygenase / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*
chemical_list: D012701:Serotonin; C522721:PHD1 protein, mouse; D011393:Procollagen-Proline Dioxygenase