抑制人类胸腺细胞中的脱氧核苷激酶可防止 dATP 积累并诱导细胞凋亡。
Inhibition of deoxynucleoside kinases in human thymocytes prevents dATP accumulation and induction of apoptosis.
作者信息
Joachims Michelle L, Marble Patrick, Knott-Craig Christopher, Pastuszko Peter, Blackburn Michael R, Thompson Linda F
机构信息
Department of Immunobiology and Cancer, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA.
出版信息
Nucleosides Nucleotides Nucleic Acids. 2008 Jun;27(6):816-20. doi: 10.1080/15257770802146270.
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.
缺乏腺苷脱氨酶（ADA）活性（一种嘌呤代谢酶）的胸腺细胞在发育过程中会在细胞内积累dATP，进而发生凋亡。我们分析了ADA酶抑制对人胸腺细胞悬浮培养物中细胞内dATP积累和凋亡诱导的影响。我们证明，虽然抑制脱氧胞苷激酶将在很大程度上阻止dATP的积累和凋亡诱导，但同时抑制脱氧胞苷激酶和腺苷激酶则完全消除了dATP的积累，并显著降低了凋亡诱导。因此，两种脱氧核苷激酶都参与了这种ADA缺乏模型。
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