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脱氧腺苷对T和B淋巴母细胞产生不同毒性的生化基础:5'-核苷酸酶的作用

Biochemical basis for differential deoxyadenosine toxicity to T and B lymphoblasts: role for 5'-nucleotidase.

作者信息

Wortmann R L, Mitchell B S, Edwards N L, Fox I H

出版信息

Proc Natl Acad Sci U S A. 1979 May;76(5):2434-7. doi: 10.1073/pnas.76.5.2434.

DOI:10.1073/pnas.76.5.2434
PMID:221924
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC383616/
Abstract

Deoxyadenosine metabolism was investigated in cultured human cells to elucidate the biochemical basis for the sensitivity of T lymphoblasts and the resistance of B lymphoblasts to deoxyadenosine toxicity. T lymphoblasts have a 20-to 45-fold greater capacity to synthesize deoxyadenosine nucleotides than B lymphoblasts at deoxyadenosine concentrations of 50--300 micron. During the synthesis of dATP, T lymphoblasts accumulate large quantities of dADP, whereas B lymphoblasts do not accumulate dADP. Enzymes affecting deoxyadenosine nucleotide synthesis were assayed in these cells. No substantial differences were evident in activities of deoxyadenosine kinase (ATP: deoxyadenosine 5'-phosphotransferase, EC 2.7.1.76) or deoxyadenylate kinase [ATP:(d)AMP phosphotransferase, EC 2.7.4.11]. The activity of 5'-nucleotidase (5'-ribonucleotide phosphohydrolase, EC 3.1.3.5) was increased 44-fold for AMP and 7-fold for dAMP in B lymphoblasts. A model for the regulation of deoxyadenosine nucleotide synthesis by 5'-nucleotidase activity is proposed on the basis of the observations.

摘要

在培养的人类细胞中研究了脱氧腺苷代谢,以阐明T淋巴母细胞敏感性和B淋巴母细胞对脱氧腺苷毒性抗性的生化基础。在50 - 300微摩尔的脱氧腺苷浓度下,T淋巴母细胞合成脱氧腺苷核苷酸的能力比B淋巴母细胞大20至45倍。在dATP合成过程中,T淋巴母细胞积累大量dADP,而B淋巴母细胞不积累dADP。在这些细胞中检测了影响脱氧腺苷核苷酸合成的酶。脱氧腺苷激酶(ATP:脱氧腺苷5'-磷酸转移酶,EC 2.7.1.76)或脱氧腺苷酸激酶[ATP:(d)AMP磷酸转移酶,EC 2.7.4.11]的活性没有明显差异。B淋巴母细胞中5'-核苷酸酶(5'-核糖核苷酸磷酸水解酶,EC 3.1.3.5)的活性对于AMP增加了44倍,对于dAMP增加了7倍。基于这些观察结果,提出了一个由5'-核苷酸酶活性调节脱氧腺苷核苷酸合成的模型。

相似文献

1
Biochemical basis for differential deoxyadenosine toxicity to T and B lymphoblasts: role for 5'-nucleotidase.脱氧腺苷对T和B淋巴母细胞产生不同毒性的生化基础:5'-核苷酸酶的作用
Proc Natl Acad Sci U S A. 1979 May;76(5):2434-7. doi: 10.1073/pnas.76.5.2434.
2
Mechanism of deoxyadenosine-induced catabolism of adenine ribonucleotides in adenosine deaminase-inhibited human T lymphoblastoid cells.脱氧腺苷在腺苷脱氨酶抑制的人T淋巴母细胞中诱导腺嘌呤核糖核苷酸分解代谢的机制。
Proc Natl Acad Sci U S A. 1982 Apr;79(8):2673-7. doi: 10.1073/pnas.79.8.2673.
3
Purine metabolizing enzymes as predictors of lymphoblast sensitivity to deoxyadenosine.嘌呤代谢酶作为淋巴细胞母细胞对脱氧腺苷敏感性的预测指标。
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S-adenosylhomocysteine hydrolase inactivation and purine toxicity in cultured human T- and B-lymphoblasts.培养的人T淋巴细胞和成淋巴细胞中S-腺苷同型半胱氨酸水解酶失活与嘌呤毒性
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6
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Adv Exp Med Biol. 1979;122B:243-59. doi: 10.1007/978-1-4684-8559-2_40.
8
The potential importance of soluble deoxynucleotidase activity in mediating deoxyadenosine toxicity in human lymphoblasts.可溶性脱氧核苷酸酶活性在介导脱氧腺苷对人淋巴母细胞毒性中的潜在重要性。
J Immunol. 1981 Jan;126(1):348-52.
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Determinants of deoxyadenosine toxicity in hybrids between human T- and B- lymphoblasts as a model for the development of drug resistance in T-cell acute lymphoblastic leukemia.人T淋巴细胞和B淋巴细胞杂交细胞中脱氧腺苷毒性的决定因素,作为T细胞急性淋巴细胞白血病耐药性发展的模型
Cancer Res. 1985 Apr;45(4):1579-86.
10
Regulation of purine metabolism by plasma membrane and cytoplasmic 5'-nucleotidases.质膜和细胞质5'-核苷酸酶对嘌呤代谢的调节
Am J Physiol. 1982 Nov;243(5):C270-7. doi: 10.1152/ajpcell.1982.243.5.C270.

引用本文的文献

1
Adenosine deaminase isoenzyme levels in patients with human T-cell lymphotropic virus type 1 and human immunodeficiency virus type 1 infections.1型人类嗜T细胞病毒和1型人类免疫缺陷病毒感染患者的腺苷脱氨酶同工酶水平
Clin Diagn Lab Immunol. 1995 Sep;2(5):626-30. doi: 10.1128/cdli.2.5.626-630.1995.
2
Potential immunological action of purine nucleoside analogues.嘌呤核苷类似物的潜在免疫作用。
Drugs. 1994;47 Suppl 6:57-62. doi: 10.2165/00003495-199400476-00009.
3
Role of adenosine deaminase in the early stages of precursor T cell maturation.腺苷脱氨酶在前体T细胞成熟早期阶段的作用。
Clin Exp Immunol. 1981 Apr;44(1):152-5.
4
Resistance of pokeweed mitogen-stimulated B cells to inhibition by deoxyadenosine.商陆有丝分裂原刺激的B细胞对脱氧腺苷抑制作用的抗性。
Clin Exp Immunol. 1980 Jul;41(1):141-9.
5
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Proc Natl Acad Sci U S A. 1982 Jun;79(12):3848-52. doi: 10.1073/pnas.79.12.3848.
6
Enzyme and membrane markers in leukaemia: recent developments.白血病中的酶和膜标志物:最新进展
J Clin Pathol. 1981 Mar;34(3):254-62. doi: 10.1136/jcp.34.3.254.
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Adenosine deaminase deficiency with normal immune function. An acidic enzyme mutation.具有正常免疫功能的腺苷脱氨酶缺乏症。一种酸性酶突变。
J Clin Invest. 1983 Aug;72(2):483-92. doi: 10.1172/jci110996.
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B cells as well as T cells form deoxynucleotides from either deoxyadenosine or deoxyguanosine.B细胞和T细胞均可利用脱氧腺苷或脱氧鸟苷形成脱氧核苷酸。
Clin Exp Immunol. 1984 Apr;56(1):39-48.
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Decreased methionine synthesis in purine nucleoside-treated T and B lymphoblasts and reversal by homocysteine.嘌呤核苷处理的T和B淋巴母细胞中蛋氨酸合成减少及同型半胱氨酸的逆转作用
J Clin Invest. 1984 Oct;74(4):1262-8. doi: 10.1172/JCI111536.
10
Specific cytotoxicity of arabinosylguanine toward cultured T lymphoblasts.阿糖基鸟嘌呤对培养的T淋巴母细胞的特异性细胞毒性。
J Clin Invest. 1984 Sep;74(3):951-5. doi: 10.1172/JCI111514.

本文引用的文献

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Protein measurement with the Folin phenol reagent.使用福林酚试剂进行蛋白质测定。
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Purinogenic immunodeficiency diseases: selective toxicity of deoxyribonucleosides for T cells.嘌呤生成性免疫缺陷疾病:脱氧核糖核苷对T细胞的选择性毒性。
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Deoxyadenosine metabolism and cytotoxicity in cultured mouse T lymphoma cells: a model for immunodeficiency disease.培养的小鼠T淋巴瘤细胞中的脱氧腺苷代谢与细胞毒性:一种免疫缺陷疾病模型
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