Apoptosis induced by prolonged exposure to odorants in cultured cells from rat olfactory epithelium.
Multicellular organisms undergo programmed cell death (PCD) as a mechanism for tissue remodeling during development and tissue renewal throughout adult life. Overdose of some neuronal receptor agonists like glutamate can trigger a PCD process termed excitotoxicity in neurons of the central nervous system. Calcium has an important role in PCD processes, especially in excitotoxicity. Since the normal turnover of olfactory receptor neurons (ORNs) relies, at least in part, on an apoptotic mechanism and odor transduction in ORNs involves an increase in intracellular Ca2+ concentration ([Ca2+]i), we investigated the possibility that long-term exposures to odorants could trigger an excitotoxic process in olfactory epithelial cells (EC). We used single-cell [Ca2+]i determinations and fluorescence microscopy techniques to study the effects of sustained odorant exposures in olfactory EC in primary culture. Induction of PCD was evaluated successively by three independent criteria: (1) measurements of DNA fragmentation, (2) translocation of phosphatidylserine to the external leaflet of the plasma membrane, and (3) caspase-3 activation. Our results support the notion of an odorant-induced PCD in olfactory EC. This odorant-induced PCD was prevented by LY83583, an odorant response inhibitor, suggesting that ORNs are the main epithelial cell population undergoing odorant-induced PCD.
Brauchi
Sebastian
S
Instituto de Quimica, Pontificia Universidad Catolica de Valparaiso, Casilla 4059, Valparaiso, Chile.
Cea
Christian
C
Farias
Jorge G
JG
Bacigalupo
Juan
J
Reyes
Juan G
JG
D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D054815:Cyclic Nucleotide-Gated Cation Channels; D053938:DNA Fragmentation / Q000187:drug effects; D004789:Enzyme Activation / Q000502:physiology; D007150:Immunohistochemistry; D007473:Ion Channels / Q000037:antagonists & inhibitors; D008856:Microscopy, Fluorescence; D009812:Odorants; D009831:Olfactory Mucosa / Q000166:cytology*; D018034:Olfactory Receptor Neurons / Q000187:drug effects; D010718:Phosphatidylserines / Q000378:metabolism; D051381:Rats
D000634:Aminoquinolines; D017304:Annexin A5; D054815:Cyclic Nucleotide-Gated Cation Channels; D007473:Ion Channels; D010718:Phosphatidylserines; C041715:6-anilino-5,8-quinolinedione; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D002118:Calcium