Buthionine sulfoximine-induced cytostasis does not correlate with glutathione depletion

Yujian Kang, M. D. Enger

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The effects of L-buthionine-(S,R)-sulfoximine (BSO) on the proliferation of normal rat kidney fibroblasts (NRK-49F) were determined and compared with the effects of BSO on cellular glutathione (GSH) content. The proliferation rate of exponentially growing NRK-49F cells was found to be slowed in 0.01 and 0.1 mM BSO and arrested in 1.0 and 10 mM BSO. There is no retardation in the proliferation of cells cultured in 0.001 mM BSO. However, varying BSO concentrations at and above 0.1 mM did not result in concordant differences in the rate and extent of GSH depletion. A dose-dependent effect of BSO on GSH levels was observed at BSO concentrations ≤0.01 mM. BSO was found also to inhibit epidermal growth factor (EGF)-induced DNA synthesis in NRK-49F cells arrested by serum deprivation in a dose-dependent pattern dissimilar to that of BSO-induced cellular GSH depletion. Removal of BSO allowed cells to resume proliferation. Further, growth-arresting BSO treatments were found to affect neither cell viability nor colony-forming efficiency. Addition of exogenous GSH or cysteine overcame BSO inhibition of EGF-induced DNA synthesis but not BSO depletion of cellular GSH levels. BSO was further found to inhibit the uptake of cysteine, cystine, and α-[1-14C]-methylaminoisobutyric acid (MeAIB) by the EGF-stimulated quiescent cells in a dose-dependent fashion. The results presented here thus demonstrate that BSO inhibits the proliferation of NRK-49F cells. This effect, however, does not correlate with BSO-induced cellular GSH depletion and is not due to an overt toxic effect. BSO-reduced amino acid uptake may represent a possible mechanism by which BSO exerts its effect on cell growth.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume262
Issue number1 31-1
StatePublished - Jan 1 1992
Externally publishedYes

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Buthionine Sulfoximine
Epidermal Growth Factor
Glutathione
Cysteine
Cystine
Poisons
DNA
Cell growth
Fibroblasts
Rats
Cells
Amino Acids
Acids
Growth
Cultured Cells
Cell Survival
Cell Proliferation
Kidney
Serum

All Science Journal Classification (ASJC) codes

  • Cell Biology
  • Clinical Biochemistry
  • Physiology

Cite this

Buthionine sulfoximine-induced cytostasis does not correlate with glutathione depletion. / Kang, Yujian; Enger, M. D.

In: American Journal of Physiology - Cell Physiology, Vol. 262, No. 1 31-1, 01.01.1992.

Research output: Contribution to journalArticle

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