title: Glutamine prevents apoptosis in intestinal epithelial cells and induces differential protective pathways in heat and oxidant injury models.
abstract: BACKGROUND
  Glutamine (GLN) can decrease mortality and length of hospital stay in the critically ill. GLN protects via enhancing protective heat shock proteins (HSPs) in heat stress (HS). GLN's effect on HSPs in oxidant injury and apoptosis remains to be elucidated. The purpose of this study was to determine if GLN protects via decreasing apoptosis during both heat and oxidative stress.
  
  
  METHODS
  IEC-18 cells were treated (15 minutes) with 0 mM GLN (control cells [CTs]) or 8 mM GLN and exposed to either lethal injury (44°C for 50 minutes or 4 mM H(2)O(2) for 30 minutes) or nonlethal injury (43°C for 45 minutes or 600 µM H(2)O(2) for 30 minutes). Survival was determined via MTS assay. Injured groups were normalized to noninjured controls. HSPs and cleaved caspase-3 (CC3), a key mediator for apoptosis, were evaluated via Western blot following a 3-hour recovery.
  
  
  RESULTS
  MTS assays showed GLN increased survival 4- to 5-fold (P < .001 vs HS CT or H(2)O(2)). Western blot showed GLN increased all 3 HSPs in HS (P < .001 vs HS CTs) but only HSP32 during oxidant injury (P < .02 vs H(2)O(2) only). GLN decreased CC3 in both injuries (P < .03 vs non-GLN-treated cells).
  
  
  CONCLUSIONS
  GLN protects intestinal cells from both heat and oxidant injury. HSP25, 32, and 70 levels increased with GLN during HS, but in oxidant injury, only HSP32 increased, suggesting GLN's mechanism of protection may vary in different models of injury. In both injuries, GLN lowered the expression of CC3, indicating prevention of apoptosis may be a key mechanism by which GLN protects.
authors.affiliation: Department of Anesthesiology, Translational PharmacoNutrition and Pharmacology Laboratory, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado, USA. alyssa.kallweit@ucdenver.edu
authors.forename: Alyssa R
authors.initials: AR
authors.lastname: Kallweit
authors.forename: Christine Hamiel
authors.initials: CH
authors.lastname: Baird
authors.forename: Diana K
authors.initials: DK
authors.lastname: Stutzman
authors.forename: Paul E
authors.initials: PE
authors.lastname: Wischmeyer
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005973:Glutamine / Q000494:pharmacology*; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism; D006358:Hot Temperature; D006861:Hydrogen Peroxide / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology* / Q000187:drug effects; D018384:Oxidative Stress; D051381:Rats
chemical_list: D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C486114:Hspb1 protein, rat; D005973:Glutamine; D006861:Hydrogen Peroxide; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; C505410:Casp3 protein, rat; D053148:Caspase 3