Inhibition of Deoxynucleoside Kinases in Human Thymocytes Prevents dATP Accumulation and Induction of Apoptosis. Nucleosides, nucleotides & nucleic acids [Nucleosides Nucleotides Nucleic Acids] Journal article | | Title | Inhibition of Deoxynucleoside Kinases in Human Thymocytes Prevents dATP Accumulation and Induction of Apoptosis. | | Author(s) | Joachims ML, Marble P, Knott-Craig C, Pastuszko P, Blackburn MR, Thompson LF | | Institution | Department of Immunobiology and Cancer, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA. | | Source | Nucleosides Nucleotides Nucleic Acids 2008 Jun; 27(6):816-820. | | 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. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 18600545 |
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