CELL-SPECIFIC INDUCTION OF HSP72-MEDIATED PROTECTION BY GLUTAMINE AGAINST OXIDANT INJURY IN IEC18 CELLS

Glutamine is a major metabolic fuel and trophic agent for intestinal e pithelial cells that can enhance intestinal epithelial cell survival a gainst oxidant and thermal stress, possibly through the induction of h eat shock protein 72 (hsp72). In this study, we examined the: possibil ity of a direct causal relationship and tissue specificity of glutamin e-induced hsp72. Glutamine treatment of intestinal (epithelial) IEC18 cells, but not HeLa (epidermoid) cells, induces the production of hsp7 2 in a concentration-dependent fashion, without affecting the expressi on of the constitutively expressed heat shock protein, hsc73. To deter mine the specific role that hsp72 induction by glutamine plays in resi stance of IEC 18 cells to oxidant injury, stable transfected cells exp ressing an hsp72 antisense construct were established. Although therma l induction of hsp72 was blacked only partially by the antisense const ruct, glutamine induction of hsp72 was completely inhibited. This was associated with a loss of the protective effects of glutamine against oxidant-induced stress. Thus, glutamine specifically induces hsp72 in intestinal epithelial cells. which mediates cell protection against in flammation-induced stress such as oxidants.