Abstract
Heat shock proteins/stress proteins (Hsps) participate in regulation of protein synthesis and degradation and serve as general cytoprotectants, yet their role in lethal Clara cell injury is not clear. To define the pattern of Hsp expression in acute lethal Clara cell injury, mice were treated with the Clara cell-specific toxicant naphthalene (NA), and patterns of expression compared to electrophilic protein adduction and previously established organellar degradation and gluathione (GSH) depletion. In sites of lethal injury (distal bronchiole), prior to organellar degradation (1 h post-NA), protein adduction is detectable and ubiquitin, Hsp 25, Hsp 72, and heme-oxygenase 1 (HO-1) are increased. Maximal Hsp expression, protein adduction, and GSH depletion occur simultaneous (by 2-3 h) with early organelle disruption. Hsp expression is higher later (6-24 h), only in exfoliating cells. In airway sites (proximal bronchiole) with nonlethal Clara cell injury elevation of Hsp 25, 72, and HO-1 expression follows significant GSH depletion (greater than 50% 2 h post-NA). This data build upon our previous studies and we conclude that (1) in lethal (terminal bronchiole) and nonlethal (proximal bronchiole) Clara cell injury, Hsp induction is associated with the loss of GSH and increased protein adduction, and (2) in these same sites, organelle disruption is not a prerequisite for Hsp induction.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 107-118 |
| Number of pages | 12 |
| Journal | Toxicology and Applied Pharmacology |
| Volume | 192 |
| Issue number | 2 |
| DOIs | |
| State | Published - Oct 15 2003 |
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Keywords
- Clara cell
- Heat shock protein
- Naphthalene
- Protein adduct
ASJC Scopus subject areas
- Toxicology
- Pharmacology
Cite this
Pulmonary heat shock protein expression after exposure to a metabolically activated Clara cell toxicant : Relationship to protein adduct formation. / Williams, Kurt J.; Cruikshank, Michael K.; Plopper, Charles.
In: Toxicology and Applied Pharmacology, Vol. 192, No. 2, 15.10.2003, p. 107-118.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Pulmonary heat shock protein expression after exposure to a metabolically activated Clara cell toxicant
T2 - Relationship to protein adduct formation
AU - Williams, Kurt J.
AU - Cruikshank, Michael K.
AU - Plopper, Charles
PY - 2003/10/15
Y1 - 2003/10/15
N2 - Heat shock proteins/stress proteins (Hsps) participate in regulation of protein synthesis and degradation and serve as general cytoprotectants, yet their role in lethal Clara cell injury is not clear. To define the pattern of Hsp expression in acute lethal Clara cell injury, mice were treated with the Clara cell-specific toxicant naphthalene (NA), and patterns of expression compared to electrophilic protein adduction and previously established organellar degradation and gluathione (GSH) depletion. In sites of lethal injury (distal bronchiole), prior to organellar degradation (1 h post-NA), protein adduction is detectable and ubiquitin, Hsp 25, Hsp 72, and heme-oxygenase 1 (HO-1) are increased. Maximal Hsp expression, protein adduction, and GSH depletion occur simultaneous (by 2-3 h) with early organelle disruption. Hsp expression is higher later (6-24 h), only in exfoliating cells. In airway sites (proximal bronchiole) with nonlethal Clara cell injury elevation of Hsp 25, 72, and HO-1 expression follows significant GSH depletion (greater than 50% 2 h post-NA). This data build upon our previous studies and we conclude that (1) in lethal (terminal bronchiole) and nonlethal (proximal bronchiole) Clara cell injury, Hsp induction is associated with the loss of GSH and increased protein adduction, and (2) in these same sites, organelle disruption is not a prerequisite for Hsp induction.
AB - Heat shock proteins/stress proteins (Hsps) participate in regulation of protein synthesis and degradation and serve as general cytoprotectants, yet their role in lethal Clara cell injury is not clear. To define the pattern of Hsp expression in acute lethal Clara cell injury, mice were treated with the Clara cell-specific toxicant naphthalene (NA), and patterns of expression compared to electrophilic protein adduction and previously established organellar degradation and gluathione (GSH) depletion. In sites of lethal injury (distal bronchiole), prior to organellar degradation (1 h post-NA), protein adduction is detectable and ubiquitin, Hsp 25, Hsp 72, and heme-oxygenase 1 (HO-1) are increased. Maximal Hsp expression, protein adduction, and GSH depletion occur simultaneous (by 2-3 h) with early organelle disruption. Hsp expression is higher later (6-24 h), only in exfoliating cells. In airway sites (proximal bronchiole) with nonlethal Clara cell injury elevation of Hsp 25, 72, and HO-1 expression follows significant GSH depletion (greater than 50% 2 h post-NA). This data build upon our previous studies and we conclude that (1) in lethal (terminal bronchiole) and nonlethal (proximal bronchiole) Clara cell injury, Hsp induction is associated with the loss of GSH and increased protein adduction, and (2) in these same sites, organelle disruption is not a prerequisite for Hsp induction.
KW - Clara cell
KW - Heat shock protein
KW - Naphthalene
KW - Protein adduct
UR - http://www.scopus.com/inward/record.url?scp=0141459491&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0141459491&partnerID=8YFLogxK
U2 - 10.1016/S0041-008X(03)00302-8
DO - 10.1016/S0041-008X(03)00302-8
M3 - Article
C2 - 14550745
AN - SCOPUS:0141459491
VL - 192
SP - 107
EP - 118
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
SN - 0041-008X
IS - 2
ER -