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Archives of Toxicology 2004-Jun

Heat shock protein 70 in the rat nasal cavity: localisation and response to hyperthermia.

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Sharon A Simpson
David J Alexander
Celia J Reed

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Heat shock proteins (HSPs) are a group of proteins that are rapidly induced in response to physiological stress, including hyperthermia and exposure to toxicants. Thus they may provide a useful index of toxicity in in vitro systems for screening for toxicity. We have recently developed a rat nasal explant system for investigating upper respiratory tract toxicity, and the aims of this study were to localise HSP70 within the rat nasal cavity and to characterise its response to hyperthermia. Constitutively, HSP70 was found to be predominantly localised to the sustentacular cells, basal cells and Bowman's glands of the olfactory epithelium (OE), with the most intense immunohistochemical staining at levels 3 and 4 of the posterior of the rat nasal cavity. Ethmoturbinates (ETs) and liver slices were exposed to heat shock (37 degrees and 43 degrees C, respectively) for 45 min and then returned to normal culture temperatures (31 degrees and 37 degrees C, respectively) for 24 h. In ETs, HSP72 was maximally induced 4-fold at 4 h after heat shock, and levels then returned to those of control tissue. ATP concentrations were markedly decreased up to 4 h after heat shock and then returned to control levels. In contrast, HSP72 levels in liver slices increased and ATP levels decreased steadily throughout the 24 h culture period. ETs were also able to withstand a 45-min heat shock at 43 degrees C, that is 12 degrees C above normal culture temperature. Incubation of ETs with cycloheximide prior to heat shock reduced the ability of the OE to recover from heat shock at 37 degrees C. Thus the OE of the rat nasal cavity expresses HSP72, and this protein appears to play an important role in the ability of the tissue to withstand hyperthermia.

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