Selective increase of dATP pools upon activation of deoxycytidine kinase in lymphocytes: Implications in apoptosis

Gergely Keszler, T. Spasokoukotskaja, Z. Csapó, Szula Virga, M. Staub, M. Sasvári

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Stimulation of the activity of deoxycytidine kinase (dCK), the principal deoxynucleoside salvage enzyme, has been recently considered as a protective cellular response to a wide range of agents interfering with DNA repair and apoptosis. In light of this, the potential contribution of dCK activation to apoptosis induction-presumably by supplying dATP or its analogues for the apoptosome formation-deserves consideration. Two-hour exposure of human tonsillar lymphocytes to 2-chloro-deoxyadenosine (CdA) led to a two-fold activation of dCK. This activation process was inhibited by pifithrin-α, a potent inhibitor of p53. When the dNTP pools were determined, both deoxypyrimidine triphosphate and dGTP pools were reduced after the treatments, while dATP levels elevated by 62%, 77% and 50% in the CdA, aphidicolin and etoposide-treated cells, respectively. We assume that dCK activation elicited by cellular damage might be a proapoptotic factor in terms of generating dATP well before the release of cytochrome c and deoxyguanosine kinase from mitochondria.

Original languageEnglish
Pages (from-to)1335-1342
Number of pages8
JournalNucleosides, Nucleotides and Nucleic Acids
Volume23
Issue number8-9
DOIs
Publication statusPublished - 2004

Fingerprint

Deoxycytidine Kinase
Lymphocytes
Chemical activation
Apoptosis
deoxyguanosine kinase
Apoptosomes
Aphidicolin
Salvaging
Mitochondria
Etoposide
Cytochromes c
DNA Repair
Repair
Cells
DNA
Enzymes

Keywords

  • Apoptosis
  • Deoxycytidine kinase
  • DNTP pools
  • p53
  • Pifithrin-α

ASJC Scopus subject areas

  • Genetics
  • Biochemistry

Cite this

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abstract = "Stimulation of the activity of deoxycytidine kinase (dCK), the principal deoxynucleoside salvage enzyme, has been recently considered as a protective cellular response to a wide range of agents interfering with DNA repair and apoptosis. In light of this, the potential contribution of dCK activation to apoptosis induction-presumably by supplying dATP or its analogues for the apoptosome formation-deserves consideration. Two-hour exposure of human tonsillar lymphocytes to 2-chloro-deoxyadenosine (CdA) led to a two-fold activation of dCK. This activation process was inhibited by pifithrin-α, a potent inhibitor of p53. When the dNTP pools were determined, both deoxypyrimidine triphosphate and dGTP pools were reduced after the treatments, while dATP levels elevated by 62{\%}, 77{\%} and 50{\%} in the CdA, aphidicolin and etoposide-treated cells, respectively. We assume that dCK activation elicited by cellular damage might be a proapoptotic factor in terms of generating dATP well before the release of cytochrome c and deoxyguanosine kinase from mitochondria.",
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T1 - Selective increase of dATP pools upon activation of deoxycytidine kinase in lymphocytes

T2 - Implications in apoptosis

AU - Keszler, Gergely

AU - Spasokoukotskaja, T.

AU - Csapó, Z.

AU - Virga, Szula

AU - Staub, M.

AU - Sasvári, M.

PY - 2004

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N2 - Stimulation of the activity of deoxycytidine kinase (dCK), the principal deoxynucleoside salvage enzyme, has been recently considered as a protective cellular response to a wide range of agents interfering with DNA repair and apoptosis. In light of this, the potential contribution of dCK activation to apoptosis induction-presumably by supplying dATP or its analogues for the apoptosome formation-deserves consideration. Two-hour exposure of human tonsillar lymphocytes to 2-chloro-deoxyadenosine (CdA) led to a two-fold activation of dCK. This activation process was inhibited by pifithrin-α, a potent inhibitor of p53. When the dNTP pools were determined, both deoxypyrimidine triphosphate and dGTP pools were reduced after the treatments, while dATP levels elevated by 62%, 77% and 50% in the CdA, aphidicolin and etoposide-treated cells, respectively. We assume that dCK activation elicited by cellular damage might be a proapoptotic factor in terms of generating dATP well before the release of cytochrome c and deoxyguanosine kinase from mitochondria.

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