GLUTAMINE REDUCES HEAT SHOCK-INDUCED CELL-DEATH IN RAT INTESTINAL EPITHELIAL-CELLS

Glutamine supplementation is beneficial for preventing intestinal atro phy and maintaining mucosal functions in metabolically stressed patien ts. The mechanisms by which glutamine prevents mucosal atrophy remain unclear. In particular, the role of glutamine in the survival of cells under stress is unknown. Intestinal epithelial cells (IEC-6) were cul tured in media with or without supplementation of L-glutamine, A low c oncentration of L-glutamine (1.0 mmol/L) was sufficient to minimize th e percentage of floating cells under basal conditions. Heat shock at 4 3 degrees C for 90 min decreased (P < 0.001) the number of attached ce lls, while increasing (P < 0.001) the number of floating cells, which is a measurement of the extent of cell death in these cultures. Glutam ine enhanced attached cell count and diminished heat shock-induced cel l death in a dose-dependent manner, Of note, 2 mmol/L was suboptimal i n both respects, thus indicating that heat-shocked cells require highe r concentrations of glutamine for optimal cell survival. Maximal effec t was achieved with 8 mmol/L glutamine, which increased (P < 0.001) ce ll growth (indicated by the number of attached cells) and diminished ( P < 0.001) cell death (indicated by the number of floating cells). Fur ther increase of L-glutamine concentration to 12 or 20 mmol/L did not provide additional benefit in minimizing cell death, Heat shock protei n 70 (hsp 70) mRNA was induced by heat shock only in cultures suppleme nted with L-glutamine, and the induction was more consistent and great er in cultures containing higher concentrations of glutamine. Thus, gl utamine supplementation reduced heat shock-induced cell death. This ef fect, together with the maintenance of cell growth, may play a key rol e in the prevention of intestinal mucosal atrophy.