title: Purinergic receptor antagonists inhibit odorant-induced heat shock protein 25 induction in mouse olfactory epithelium.
abstract: Heat shock proteins (HSPs) accumulate in cells exposed to a variety of physiological and environmental factors, such as heat shock, oxidative stress, toxicants, and odorants. Ischemic, stressed, and injured cells release ATP in large amounts. Our hypothesis is that noxious stimulation (in this case, strong odorant) evokes the release of ATP in the olfactory epithelium (OE). Extracellular ATP, a signal of cellular stress, induces the expression of HSPs via purinergic receptors. In the present study, in vivo odorant exposure (heptanal or R-carvone) led to a selective induction of HSP25 in glia-like sustentacular cells in the Swiss Webster mouse OE, as previously shown in rats (Carr et al., 2001). Furthermore, in vitro and in vivo administration of purinergic receptor antagonists suramin and pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) blocked the expression of HSP25 immunoreactivity in sustentacular cells. ATP released by acutely injured cells could act as an early signal of cell and tissue damage, causing HSP expression and initiating a stress signaling cascade to protect against further damage. Sustentacular cells have a high capacity to detoxify xenobiotics and thereby protect the olfactory epithelium from airborne pollutants. Thus, the robust, rapid induction of HSPs in sustentacular cells may help maintain the integrity of the OE during exposure to toxicants.
authors.affiliation: Department of Physiology, University of Utah, Salt Lake City, Utah 84108-1297, USA. c.hegg@m.cc.utah.edu
authors.forename: Colleen C
authors.initials: CC
authors.lastname: Hegg
authors.forename: Mary T
authors.initials: MT
authors.lastname: Lucero
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D003952:Diagnostic Imaging; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D007150:Immunohistochemistry; D049449:Luminescence; D051379:Mice; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009812:Odorants; D009831:Olfactory Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D058914:Purinergic Antagonists; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D006360:Heat-Shock Proteins; C486113:Hsbp1 protein, mouse; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D058914:Purinergic Antagonists; D000255:Adenosine Triphosphate; D002118:Calcium