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Nucleosides Nucleotides Nucleic Acids. 2008 Jun;27(6):816-20. doi: 10.1080/15257770802146270.

Inhibition of deoxynucleoside kinases in human thymocytes prevents dATP accumulation and induction of apoptosis.

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1
Department of Immunobiology and Cancer, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA. Michelle-Joachims@omrf.org

Abstract

Thymocytes lacking adenosine deaminase (ADA) activity, a purine metabolism enzyme, accumulate intracellular dATP and consequently undergo apoptosis during development. We have analyzed the effect of ADA enzyme inhibition in human thymocyte suspension cultures with regard to accumulation of intracellular dATP and induction of apoptosis. We demonstrate that while inhibition of deoxycytidine kinase will prevent the accumulation of dATP and induction of apoptosis to a large degree, inhibition of both deoxycytidine kinase and adenosine kinase completely abrogates the accumulation of dATP and significantly reduces the induction of apoptosis. Thus, both deoxynucleoside kinases are involved in this model of ADA deficiency.

PMID:
18600545
PMCID:
PMC2752032
DOI:
10.1080/15257770802146270
[Indexed for MEDLINE]
Free PMC Article
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