人T淋巴细胞中2',3'-二脱氧腺苷代谢的生化遗传学分析。

Biochemical genetic analysis of 2',3'-dideoxyadenosine metabolism in human T lymphocytes.

作者信息

Carson D A, Haertle T, Wasson D B, Richman D D

机构信息

Department of Basic and Clinical Research, Scripps Clinic and Research Foundation, La Jolla, California 92037.

出版信息

Biochem Biophys Res Commun. 1988 Mar 15;151(2):788-93. doi: 10.1016/s0006-291x(88)80350-4.

DOI:10.1016/s0006-291x(88)80350-4

PMID:3258154

Abstract

2',3'-dideoxyadenosine (ddAdo) has been shown to inhibit the infection of cultured human T lymphoblasts with the human immunodeficiency virus-1 (HIV-1). However, the pathways of ddAdo metabolism in T lymphocytes have not been well defined. We have studied the uptake and degradation of ddAdo in human CEM T lymphoblasts, in mutant CEM T cells deficient in adenosine kinase or deoxycytidine kinase, and in normal lymphocytes and monocytes. The results indicate that ddAdo may be phosphorylated in T cells by several different enzymes, although deoxycytidine kinase predominates. However, 99% of the ddAMP formed is deaminated by AMP deaminase and subsequently dephosphorylated. Thus, the ability of ddAdo to prevent HIV-1 infection may be limited in cells with high AMP deaminase activity.

摘要

已证明2',3'-二脱氧腺苷（ddAdo）可抑制培养的人T淋巴母细胞感染人免疫缺陷病毒1型（HIV-1）。然而，T淋巴细胞中ddAdo的代谢途径尚未明确。我们研究了ddAdo在人CEM T淋巴母细胞、缺乏腺苷激酶或脱氧胞苷激酶的突变型CEM T细胞以及正常淋巴细胞和单核细胞中的摄取和降解。结果表明，尽管脱氧胞苷激酶起主要作用，但ddAdo在T细胞中可能被几种不同的酶磷酸化。然而，所形成的ddAMP中有99%被AMP脱氨酶脱氨，随后去磷酸化。因此，在具有高AMP脱氨酶活性的细胞中，ddAdo预防HIV-1感染的能力可能有限。