Background. Eukaryotic organisms possess natural defense mechanisms that protect against stress stimuli. One such mechanism is the activation of families of stress response genes (e.g., the acute phase response). Transcription of many of these genes is regulated by the leucine zipper or bZIP proteins (CCAAT binding/enhancer binding proteins [C/EBPs]). The aim of this study was to show that the C/EBP transcription factor genes respond to thermal injury. Methods. Age- and weight-matched male Buffalo, Sprague- Dawley, and Fischer 344 12- to 16-week-old rats (275 to 325 gm) received a 40% total body surface area scald burn. Total RNA was isolated from livers at 0, 2, 5, 12, 24, and 48 hours. Northern blot hybridization was performed with 32P-labeled C/EBPα, C/EBPβ, and C/EBPδ cDNAs. Relative amounts of each mRNA were determined by densitometric analyses. For Western analyses liver nuclear and cytoplasmic protein extracts were prepared from burned and control rats. Nuclear protein extracts were resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, blotted onto a PVDF membrane, and detected by using an enhanced chemiluminescence detection kit. Results. Expression of C/EBP genes is regulated in response to 40% total body surface area scald burn. A simultaneous decrease in C/EBPα and an increase in C/EBPβ and C/EBPδ mRNA levels occur in response to thermal injury. Western analyses detect changes in C/EBPα and C/EBPβ pool levers that suggest a differential regulation of these genes in response to thermal injury. Conclusions. The responses of C/EBPα, C/EBPβ, and C/EBPδ are similar in Buffalo, Sprague-Dawley, and Fischer rats. The induced level, however, of C/EBPβ mRNA was highest in the Sprague-Dawley strain and lowest in the Buffalo strain and correlates well with the mortality of these strains. Because C/EBPβ is associated with the transactivation of stress response genes, this may explain the intensity of the response in the susceptible strains. This agrees with our hypothesis that the higher degree of sensitivity of the Sprague-Dawley rat to stress relative to the Buffalo strain may be due to inherently higher levels of factors such as C/EBP whose functions are associated with activation of stress response genes.
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