TY - JOUR
T1 - Inhibition of deoxynucleoside kinases in human thymocytes prevents dATP accumulation and induction of apoptosis
AU - Joachims, Michelle L.
AU - Marble, Patrick
AU - Knott-Craig, Christopher
AU - Pastuszko, Peter
AU - Blackburn, Michael R.
AU - Thompson, Linda F.
N1 - Funding Information:
This work was supported by the NIH grant HD36044 to L. F. T. L. F. T. holds the Putnam City Schools Distinguished Chair in Cancer Research. Address correspondence to Michelle L. Joachims, Department of Immunobiology and Cancer, MS 29; 825 NE 13th St., Oklahoma City, OK 73104, USA. E-mail: [email protected]
PY - 2008/6
Y1 - 2008/6
N2 - 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.
AB - 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.
KW - ADA deficiency
KW - Apoptosis
KW - Deoxynucleoside kinases
KW - Human thymocyte development
UR - http://www.scopus.com/inward/record.url?scp=46649121858&partnerID=8YFLogxK
U2 - 10.1080/15257770802146270
DO - 10.1080/15257770802146270
M3 - Article
C2 - 18600545
AN - SCOPUS:46649121858
SN - 1525-7770
VL - 27
SP - 816
EP - 820
JO - Nucleosides, Nucleotides and Nucleic Acids
JF - Nucleosides, Nucleotides and Nucleic Acids
IS - 6-7
ER -