Odorants as cell-type specific activators of a heat shock response in the rat olfactory mucosa.
Heat shock, or stress, proteins (HSPs) are induced in response to conditions that cause protein denaturation. Activation of cellular stress responses as a protective and survival mechanism is often associated with chemical exposure. One interface between the body and the external environment and chemical or biological agents therein is the olfactory epithelium (OE). To determine whether environmental odorants affect OE HSP expression, rats were exposed to a variety of odorants added to the cage bedding. Odorant exposure led to transient, selective induction of HSP70, HSC70, HSP25, and ubiquitin immunoreactivities (IRs) in supporting cells and subepithelial Bowman's gland acinar cells, two OE non-neuronal cell populations involved with inhalant biotransformation, detoxification, and maintenance of overall OE integrity. Responses exhibited odor specificity and dose dependency. HSP70 and HSC70 IRs occurred throughout the apical region of supporting cells; ubiquitin IR was confined to a supranuclear cone-shaped region. Electron microscopic examination confirmed these observations and, additionally, revealed odor-induced formation of dense vesicular arrays in the cone-like regions. HSP25 IR occurred throughout the entire supporting cell cytoplasm. In contrast to classical stress responses, in which the entire array of stress proteins is induced, no increases in HSP40 and HSP90 IRs were observed. Extended exposure to higher odorant doses caused prolonged activation of the same HSP subset in the non-neuronal cells and severe morphological damage in both supporting cells and olfactory receptor neurons (ORNs), suggesting that non-neuronal cytoprotective stress response mechanisms had been overwhelmed and could no longer adequately maintain OE integrity. Significantly, ORNs showed no stress responses in any of our studies. These findings suggest a novel role for these HSPs in olfaction and, in turn, possible involvement in other normal neurophysiological processes.
Carr
V M
VM
Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208-3520, USA. v-carr@northwestern.edu
Menco
B P
BP
Yankova
M P
MP
Morimoto
R I
RI
Farbman
A I
AI
D000447:Aldehydes / Q000008:administration & dosage; D000818:Animals; D020148:Butyric Acid / Q000008:administration & dosage; D050883:HSC70 Heat-Shock Proteins; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins; D018869:Heat-Shock Response / Q000502:physiology*; D007150:Immunohistochemistry; D019570:Inhalation Exposure; D008297:Male; D008854:Microscopy, Electron; D009363:Neoplasm Proteins / Q000378:metabolism; D009812:Odorants; D009822:Oils, Volatile / Q000008:administration & dosage; D009831:Olfactory Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D018034:Olfactory Receptor Neurons / Q000166:cytology / Q000378:metabolism; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012862:Skatole / Q000008:administration & dosage; D013268:Stimulation, Chemical; D013438:Sulfhydryl Compounds / Q000008:administration & dosage; D013729:Terpenes / Q000008:administration & dosage; D014452:Ubiquitins / Q000378:metabolism
D000447:Aldehydes; D050883:HSC70 Heat-Shock Proteins; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C494373:Hspa8 protein, rat; C486114:Hspb1 protein, rat; D009363:Neoplasm Proteins; D009822:Oils, Volatile; D013438:Sulfhydryl Compounds; D013729:Terpenes; D014452:Ubiquitins; D020148:Butyric Acid; D012862:Skatole