TIME-COURSE CHANGES IN NUCLEAR TRANSLOCATION OF HEPATIC GLUCOCORTICOID RECEPTOR IN RATS AFTER BURN TRAUMA AND ITS PATHOPHYSIOLOGICAL SIGNIFICANCE

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Abstract

ABSTRACT

Nuclear translocation is a determining step for the glucocorticoid receptor (GR) to exert its functions in response to traumatic conditions. This study was designed to observe the nuclear translocation changes of hepatic GR in severely burned rats during early postburn stage, and to explore the effects of high-dose dexamethasone on GR nuclear translocation. Rats with 35% total body surface area full-thickness burn injury, parallelized with a sham-burn group, were killed at consecutive time points to examine the changes in plasma corticosterone and expression of hepatic GR at both whole-cell and nuclear levels. The effects of high-dose dexamethasone on GR nuclear translocation and suppression of proinflammatory cytokine overproduction were subsequently analyzed. In burned rats, plasma corticosterone increased remarkably soon after burn injury. On the contrary, the hepatic GR levels showed an initial phase of decrease as measured in both whole-cell and nucleus by Western blot, followed by a rapid elevation in the nucleus but a slow recovery at whole-cell level. By comparing the changes of GR in both whole-cell and nuclear levels, we found that GR nuclear translocation was relatively enhanced in the early postburn period. High-dose dexamethasone administered at 1 or 48 h postburn did not further elevate GR nuclear translocation, neither did it restrain the increased release of proinflammatory cytokines such as TNF-α and IL-1β. These studies suggest that although the whole-cell level of hepatic GR is decreased, GR nuclear translocation is relatively enhanced at early postburn stage. High-dose exogenous glucocorticoids may not promote more nuclear translocation of GR to reinforce its functions.

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