INDUCTION OF GLUTAMINE-SYNTHETASE EXPRESSION AFTER MAJOR BURN INJURY IS TISSUE-SPECIFIC AND TEMPORALLY VARIABLE

Background: Major burn injury results in a translocation of amino acid s from peripheral tissues to the abdominal viscera. Glutamine is a maj or participant in this event. Thermal injury causes a depletion of pla sma and muscle glutamine pools as well as activation of proteolysis an d release of glutamine from skeletal muscle. De novo synthesis of glut amine is regulated by the expression of the enzyme glutamine synthetas e (GS), We studied the tissue-specific regulation of GS expression aft er thermal injury. Methods: Burn injury of rats was produced by scaldi ng of 25 or 40% of skin surface. In normal rats, four organs, includin g lung, muscle, kidney, and liver were assayed for relative GS messeng er RNA content by Northern blotting 8 and 24 hours after 40% area burn . The effect of adrenalectomy on GS mRNA induction Results: GS mRNA le vels were increased 2.3-fold in lung at 8 hours and 7.3-fold in muscle at 24 hours after burn injury. No appreciable increase in GS mRNA lev el was observed in kidney or liver. Muscle GS mRNA levels were lower t han sham-operated controls in both burned and unburned adrenalectomize d rats. However, adrenalectomy did not attenuate relative GS mRNA indu ction in muscle at 24 hours after burn injury. Conclusions: Burn injur y causes an induction in GS mRNA levels in a tissue-specific fashion. Adrenalectomy greatly reduced GS mRNA levels, but did not completely b lock the induction of GS express in muscle after burn injury. This fin ding suggests that glucocorticoid hormones together with a unknown fac tor of nonadrenal origin influence this metabolic response to burn inj ury.