Reduced stress tolerance of glutamine-deprived human monocytic cells is associated with selective down-regulation of Hsp70 by decreased mRNA stability.
In critically ill patients, clinicians observe a reverse correlation of survival and a decreased plasma concentration of the most abundant free amino acid, glutamine (Gln). However, in this context, the role of Gln remains largely elusive. Gln is used as an energy substrate by monocytes. Gln deprivation of these cells results in an increased susceptibility to cell stress and apoptosis, as well as in a reduced responsiveness to pro-inflammatory stimuli. We performed a systematic study to elucidate the molecular mechanism by which Gln depletion affects the heat stress response of the monocytic cell line U937. Proteomic analysis revealed that Gln depletion was associated with specific changes in the protein expression pattern. However, the overall level of tRNA-bound Gln remained unaffected. The stress protein heat shock protein (Hsp) 70 showed the highest reduction in protein synthesis. This was due to enhanced mRNA decay during Gln starvation while the transcriptional and the translational control of Hsp70 expression remained unchanged. A physiological Gln concentration and above was found to be necessary for maximum Hsp70 accumulation upon heat shock. Thus, the study shows a specific link between Gln metabolism and the regulation of heat shock proteins.
Eliasen
Maja Munk
MM
Department of Surgery-Research Laboratories, Medical University of Vienna, AKH (8G9.05), Waehringer-Guertel 18-20, 1090, Vienna, Austria. rudolf.oehler@meduniwien.ac.at
Brabec
Marianne
M
Gerner
Christopher
C
Pollheimer
Jürgen
J
Auer
Herbert
H
Zellner
Maria
M
Weingartmann
Gertrude
G
Garo
Fritz
F
Roth
Erich
E
Oehler
Rudolf
R
D002478:Cells, Cultured; D015536:Down-Regulation; D005973:Glutamine / Q000172:deficiency* / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D009000:Monocytes / Q000378:metabolism*; D011132:Polyribosomes / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013696:Temperature; D013997:Time Factors
D018840:HSP70 Heat-Shock Proteins; D012333:RNA, Messenger; D005973:Glutamine