Rescue of cells from apoptosis by inhibition of active GSH extrusion

L. Ghibelli, C. Fanelli, G. Rotilio, E. Lafavia, S. Coppola, C. Colussi, P. Civitareale, M. R. Ciriolo

Research output: Contribution to journalArticle

286 Citations (Scopus)

Abstract

Cells induced to apoptosis extrude glutathione in the reduced form concomitantly with (U937 cells) or before (HepG2 cells) the development of apoptosis, much earlier than plasma membrane leakage. Two specific inhibitors of carrier-mediated GSH extrusion, methionine or cystathionine, are able to decrease apoptotic GSH efflux across the intact plasma membrane, demonstrating that in these cell systems GSH extrusion occurs via a specific mechanism. While decreasing GSH efflux, cystathionine or methionine also decrease the extent of apoptosis. They fail to exert anti-apoptotic activity in cells previously deprived of GSH, indicating that the target of the protection is indeed GSH efflux. The cells rescued by methionine or cystathionine remained viable after removal of the apoptogenic inducers and were even able to replicate. This shows that a real rescue to perfect viability and not just a delay of apoptosis is achieved by forcing GSH to stay within the cells during apoptogenic treatment. All this evidence indicates that extrusion of reduced glutathione precedes and is responsible for the irreversible morphofunctional changes of apoptosis, probably by altering the intracellular redox state without intervention of reactive oxygen species, thus giving a rationale for the development of redox- dependent apoptosis under anaerobic conditions.

Original languageEnglish
Pages (from-to)479-486
Number of pages8
JournalFASEB Journal
Volume12
Issue number6
Publication statusPublished - 1998

Fingerprint

extrusion
Extrusion
apoptosis
Cystathionine
Apoptosis
cystathionine
Methionine
methionine
cells
Cell membranes
Oxidation-Reduction
Glutathione
glutathione
Cell Membrane
plasma membrane
U937 Cells
Hep G2 Cells
Reactive Oxygen Species
anaerobic conditions
reactive oxygen species

Keywords

  • Cystathionine
  • GSH efflux
  • Methionine
  • Puromycin

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Ghibelli, L., Fanelli, C., Rotilio, G., Lafavia, E., Coppola, S., Colussi, C., ... Ciriolo, M. R. (1998). Rescue of cells from apoptosis by inhibition of active GSH extrusion. FASEB Journal, 12(6), 479-486.

Rescue of cells from apoptosis by inhibition of active GSH extrusion. / Ghibelli, L.; Fanelli, C.; Rotilio, G.; Lafavia, E.; Coppola, S.; Colussi, C.; Civitareale, P.; Ciriolo, M. R.

In: FASEB Journal, Vol. 12, No. 6, 1998, p. 479-486.

Research output: Contribution to journalArticle

Ghibelli, L, Fanelli, C, Rotilio, G, Lafavia, E, Coppola, S, Colussi, C, Civitareale, P & Ciriolo, MR 1998, 'Rescue of cells from apoptosis by inhibition of active GSH extrusion', FASEB Journal, vol. 12, no. 6, pp. 479-486.
Ghibelli L, Fanelli C, Rotilio G, Lafavia E, Coppola S, Colussi C et al. Rescue of cells from apoptosis by inhibition of active GSH extrusion. FASEB Journal. 1998;12(6):479-486.
Ghibelli, L. ; Fanelli, C. ; Rotilio, G. ; Lafavia, E. ; Coppola, S. ; Colussi, C. ; Civitareale, P. ; Ciriolo, M. R. / Rescue of cells from apoptosis by inhibition of active GSH extrusion. In: FASEB Journal. 1998 ; Vol. 12, No. 6. pp. 479-486.
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