Inhibition of glutamine synthetase in A549 cells during hyperoxia

Sharon A McGrath-Morrow, Jennifer Stahl

Research output: Contribution to journalArticle

Abstract

High oxygen concentrations are used in the treatment of acute respiratory distress syndrome and hyaline membrane disease. Hyperoxia, however, can damage alveolar epithelial cells through the release of free oxygen radicals. Supplemental glutamine (Gln) has recently been shown to increase survival of A549 cells, a distal epithelial cell line, during hyperoxia (1). We found that supplemental Gln (Gln+) is essential for cell growth in A549 cells. In room air, cells without supplemental Gln (Gln-) survived with BCL-2 levels similar to those of Gln+ cells, but cell growth was minimal. We also evaluated the role of glutamine synthetase (GS) in A549 cells during hyperoxia. L-methionine sulfoximine (MSO), an irreversible inhibitor of GS, was added to Gln+ and Gln- cells. In hyperoxia, Gln-cells had greater survival then Gln- cells treated with MSO. Supplemental Gln could rescue cells in hyperoxia from the effect of MSO, suggesting that GS, through the endogenous synthesis of Gln, could attenuate hyperoxic cell injury. In hyperoxia, cells treated with 10-mM concentrations of Gln had increased survival compared with cells receiving 2-mM concentrations. The higher concentration of Gln, however, did not decrease the percentage of cells undergoing necrosis.

Original languageEnglish (US)
Pages (from-to)99-106
Number of pages8
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume27
Issue number1
StatePublished - 2002

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Glutamate-Ammonia Ligase
Hyperoxia
Glutamine
Methionine Sulfoximine
Methionine
Cell growth
A549 Cells
Hyaline Membrane Disease
Alveolar Epithelial Cells
Adult Respiratory Distress Syndrome
Growth
Free Radicals
Reactive Oxygen Species

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Pulmonary and Respiratory Medicine

Cite this

Inhibition of glutamine synthetase in A549 cells during hyperoxia. / McGrath-Morrow, Sharon A; Stahl, Jennifer.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 27, No. 1, 2002, p. 99-106.

Research output: Contribution to journalArticle

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