Protective effect of glutamine on endothelial cell ATP in oxidant injury.
Endothelial cell dysfunction following exposure to H2O2 is associated with rapid inhibition of glucose-dependent pathways of ATP synthesis. The role other substrates for ATP synthesis (e.g., amino acids) may play in the metabolism of H2O2-injured cells is unclear. The effect of glutamine, a precursor of the Kreb's cycle intermediate alpha-ketoglutarate on ATP levels in bovine pulmonary artery endothelial cells exposed to H2O2 was examined. The presence of glutamine during H2O2 injury significantly enhanced ATP levels in the injured cells. Concentrations of glutamine as low as 50 microM produced significant improvement of ATP levels in endothelial cells exposed to 5 mM H2O2. The 2 mM concentration of glutamine produced the greatest benefit, while greater concentrations of glutamine (5-20 mM) were actually associated with progressive decrements of the maximal benefit seen with the 2 mM concentration. The 2 mM concentration of glutamine produced similar enhancement of ATP with 1 and 10 mM H2O2 injury as well. Short-term viability following 5 mM H2O2 injury was significantly improved by the presence of 2 mM glutamine. The most effective concentration of glutamine (2 mM) did not scavenge H2O2 in a fluorometric assay. These observations suggest that mitochondrial substrates, such as glutamine, that bypass glucose-dependent pathways of ATP synthesis may be useful therapeutic agents for maintenance of ATP levels in oxidant-injured cells.
Surgical Service, Ann Arbor VA Medical Center, Michigan 48105.
D B
DB
Hinshaw
J M
JM
Burger
D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000818:Animals; D002417:Cattle; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005973:Glutamine / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D011651:Pulmonary Artery
D005973:Glutamine; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide