title: Adaptive cellular mechanisms in response to glutamine-starvation.
abstract: Glutamine (Gln) utilising cells suffer from Gln-starvation during critical illness when plasma Gln levels are decreased. This study investigates whether such cells activate adaptive mechanisms. Monocytic U937 cells were cultured at 0.6 and 0.2 mM Gln for up to four days. Within the first day a decrease of ATP (78% of control), intracellular free Gln (13%), Hsp70 (74%) and proliferation rate (79%) was observed. A prolonged culture at 0.6 mM Gln for additional three days led to a recovery of ATP (97%), Hsp70 (91%) and proliferation (92%). The intracellular free Gln increased only to 41%. At 0.2 mM Gln, however, all levels remained decreased. The activation of the metabolic sensor AMP activated kinase (AMPK) increased immediately in Gln-starving cells but regained normal values only in cells cultured at 0.6 mM. A proteomic analysis identified 23 proteins, which were affected by Gln starvation including metabolic enzymes, proteins involved in synthesis and degradation of RNA and proteins, and stress proteins. These data show that Gln-utilising cells activate adaptive mechanisms in response to Gln-starvation, which enable them to overcome a Gln shortage. At very low Gln concentrations, these adaptive mechanisms are not sufficient to countervail the lack of the amino acid.
authors.affiliation: Department of Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Maja Munk
authors.initials: MM
authors.lastname: Eliasen
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Winkler
authors.forename: Veronika
authors.initials: V
authors.lastname: Jordan
authors.forename: Marion
authors.initials: M
authors.lastname: Pokar
authors.forename: Martina
authors.initials: M
authors.lastname: Marchetti
authors.forename: Erich
authors.initials: E
authors.lastname: Roth
authors.forename: Günter
authors.initials: G
authors.lastname: Allmaier
authors.forename: Rudolf
authors.initials: R
authors.lastname: Oehler
mesh_terms: D000222:Adaptation, Physiological; D018929:Cell Culture Techniques; D016638:Critical Illness; D015180:Electrophoresis, Gel, Two-Dimensional; D005973:Glutamine / Q000378:metabolism*; D005978:Glutathione / Q000032:analysis; D006801:Humans; D009000:Monocytes / Q000378:metabolism*; D014176:Protein Biosynthesis; D011506:Proteins / Q000032:analysis; D040901:Proteomics; D013217:Starvation / Q000378:metabolism*
chemical_list: D011506:Proteins; D005973:Glutamine; D005978:Glutathione