Glutathione depletion and disruption of intracellular ionic homeostasis regulate lymphoid cell apoptosis

Rodrigo Franco-Cruz, Wayne I. DeHaven, Maria I. Sifre, Carl D. Bortner, John A. Cidlowski

Research output: Contribution to journalArticle

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Abstract

Intracellular glutathione (GSH) depletion is an important hallmark of apoptosis. We have recently shown that GSH depletion by its extrusion regulates apoptosis independently of excessive reactive oxygen species accumulation. However, the mechanisms by which GSH depletion regulates apoptosis are still unclear. Because disruption of intracellular ionic homeostasis, associated with apoptotic volume decrease (AVD), is necessary for the progression of apoptotic cell death, we sought to evaluate the relationship between GSH transport and ionic homeostasis during Fas ligand (FasL)-induced apoptosis in Jurkat cells. GSH depletion in response to FasL was paralleled by distinct degrees of AVD identified by differences in cellular forward scatter and electronic impedance analysis. Inhibition of GSH efflux prevented AVD, K+ loss, and the activation of two distinct ionic conductances, mediated by Kv1.3 and outward rectifying Cl- channels. Reciprocally, stimulation of GSH loss accelerated the loss of K+, AVD, and consequently the progression of the execution phase of apoptosis. Although high extracellular K+ inhibited FasL-induced apoptosis, GSH depletion was largely independent of K+ loss. These results suggest that deregulation of GSH and ionic homeostasis converge in the regulation of apoptosis in lymphoid cells.

Original languageEnglish (US)
Pages (from-to)36071-36087
Number of pages17
JournalJournal of Biological Chemistry
Volume283
Issue number52
DOIs
StatePublished - Dec 26 2008

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Glutathione
Homeostasis
Lymphocytes
Apoptosis
Fas Ligand Protein
Jurkat Cells
Deregulation
Cell death
Electric Impedance
Extrusion
Reactive Oxygen Species
Cell Death
Chemical activation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Glutathione depletion and disruption of intracellular ionic homeostasis regulate lymphoid cell apoptosis. / Franco-Cruz, Rodrigo; DeHaven, Wayne I.; Sifre, Maria I.; Bortner, Carl D.; Cidlowski, John A.

In: Journal of Biological Chemistry, Vol. 283, No. 52, 26.12.2008, p. 36071-36087.

Research output: Contribution to journalArticle

Franco-Cruz, Rodrigo ; DeHaven, Wayne I. ; Sifre, Maria I. ; Bortner, Carl D. ; Cidlowski, John A. / Glutathione depletion and disruption of intracellular ionic homeostasis regulate lymphoid cell apoptosis. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 52. pp. 36071-36087.
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