Document Detail


Effects of deoxyadenosine on ribonucleotide reductase in adenosine deaminase-deficient lymphocytes.
MedLine Citation:
PMID:  1830628     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
To explore the relationship between ribonucleotide reductase and immunodysfunction in adenosine deaminase deficiency, the effects of deoxyadenosine on ribonucleotide reductase in ADA-deficient lymphocytes was investigated. An assay system for ribonucleotide reductase in intact permeabilized lymphocytes was developed to approximate physiological conditions. The activity of cytidine diphosphate (CDP) reductase in resting but not in proliferating lymphocytes in culture was inhibited by 1 to 10 mumol/L deoxyadenosine. The resting cells were protected from the toxicity of 1 mumol/L deoxyadenosine by 5 mmol/L nicotinamide or 30 mumol/L deoxycytidine and from that of 10 mumol/L deoxyadenosine by 30 mumol/L deoxycytidine. These findings suggest that depletion of nicotinamide adenine dinucleotide might be the principal cause of death in resting lymphocytes with ADA deficiency. It is concluded that the mechanism of deoxyadenosine toxicity on non-replicating lymphocytes, which may not be mediated by ribonucleotide reductase inhibition, is closely related to the mechanism of immunodysfunction in patients with ADA deficiency.
Authors:
E Takeda; Y Kuroda; E Naito; I Yokota; T Saijo; M Hirose; M Miyao
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of inherited metabolic disease     Volume:  14     ISSN:  0141-8955     ISO Abbreviation:  J. Inherit. Metab. Dis.     Publication Date:  1991  
Date Detail:
Created Date:  1991-09-03     Completed Date:  1991-09-03     Revised Date:  2007-03-21    
Medline Journal Info:
Nlm Unique ID:  7910918     Medline TA:  J Inherit Metab Dis     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  87-95     Citation Subset:  IM    
Affiliation:
Department of Paediatrics, School of Medicine, University of Tokushima, Japan.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Deaminase / deficiency*
Cell Division / drug effects
Cell Membrane Permeability
Coformycin / pharmacology
Cytidine Diphosphate / pharmacology
Deoxyadenosines / pharmacology*
Dipyridamole / pharmacology
Humans
Kinetics
Lymphocytes / drug effects,  enzymology*
Niacinamide / pharmacology
Phytohemagglutinins / pharmacology
Ribonucleoside Diphosphate Reductase / metabolism
Ribonucleotide Reductases / antagonists & inhibitors*
Chemical
Reg. No./Substance:
0/Deoxyadenosines; 0/Phytohemagglutinins; 11033-22-0/Coformycin; 58-32-2/Dipyridamole; 63-38-7/Cytidine Diphosphate; 98-92-0/Niacinamide; EC 1.17.4.-/CDP reductase; EC 1.17.4.-/Ribonucleotide Reductases; EC 1.17.4.1/Ribonucleoside Diphosphate Reductase; EC 3.5.4.4/Adenosine Deaminase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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