Glutathione stimulates A549 cell proliferation in glutamine‐deficient culture

The effect of glutamate supplementation

Yujian Kang, Yi Feng, Emiko L. Hatcher

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Extracellular glutathione (GSH) is degraded by an external cell‐surface enzyme, γ‐glutamyltranspeptidase (γ‐GT). The products are transported into cells to participate in important cellular processes. In the present study, we tested the hypothesis that extracellular GSH is a source of glutamic acid for cells that express γ‐GT. Under a glutamine‐deficient culture condition, the extracellular GSH‐supplemented glutamic acid would enhance intracellular glutamine synthesis, thereby stimulating cell proliferation. Human lung carcinoma A549 cells were cultured in glutamine‐deficient Dulbecco's modified Eagle medium, and they did not proliferate unless glutamine was supplemented. Extracellular GSH, however, provoked a partial proliferation. The GSH effect correlated with a high level of γ‐GT activity and an increased intracellular level of glutamic acid. A constituent amino acid of GSH, glutamic acid but not cysteine, produced the same growth‐stimulatory effect as GSH. Furthermore, neither oxothiazolidine‐4‐carboxylate (OTC), a celluar cysteine‐delivery compound, nor cysteinylglycine, a dipeptide released from the γ‐GT reaction, stimulated cell proliferation. Moreover, buthionine sulfoximine (BSO), a selective inhibitor of γ‐glutamylcysteine synthetase, enhanced the GSH growth stimulatory effect, suggesting that increased cellular GSH synthesis does not correlate with cell growth stimulation. The results obtained demonstrated that glutamine is required for A549 cell proliferation and exogenous GSH partially substitutes for the growth stimulatory action of glutamine. It also suggests that the glutamic acid rather than the cysteine released from the GSH is responsible for the cell proliferation. © 1994 Wiley‐Liss, Inc.

Original languageEnglish (US)
Pages (from-to)589-596
Number of pages8
JournalJournal of Cellular Physiology
Volume161
Issue number3
DOIs
StatePublished - Jan 1 1994
Externally publishedYes

Fingerprint

Cell proliferation
Cell culture
Glutathione
Glutamic Acid
Glutamine
Cell Proliferation
cysteinylglycine
Cysteine
Growth
Glutamate-Cysteine Ligase
Buthionine Sulfoximine
Eagles
Dipeptides
Cell growth
A549 Cells
Carcinoma
Amino Acids
Lung
Enzymes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Glutathione stimulates A549 cell proliferation in glutamine‐deficient culture : The effect of glutamate supplementation. / Kang, Yujian; Feng, Yi; Hatcher, Emiko L.

In: Journal of Cellular Physiology, Vol. 161, No. 3, 01.01.1994, p. 589-596.

Research output: Contribution to journalArticle

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