Suppression of human lymphocyte DNA and protein synthesis in vitro by adenosine and eight modified adenine nucleosides in the presence or in the absence of adenosine deaminase inhibitors, 2′-deoxycoformycin (DCF) and erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA)

Ratech, Howard; Kuritsky, Lloyd; Thorbecke, G. J.; Hirschhorn, Rochelle

doi:10.1016/0008-8749(82)90109-5

Cited by 7 publications

(1 citation statement)

References 25 publications

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“…Its critical role on the function, maturation, and maintenance of immunological responses has made ADA analysis an important tool, providing informative database where the disease mimics altered immunity [2]. A high attention has been paid to the correlation between serum ADA activity and diVerent immunodeWciency disorders [3][4][5]. The wide distribution of ADA in most human tissues [1] might be an indication of its involvement in diVerent diseases and disorders.…”

Section: Introductionmentioning

confidence: 99%

Serum adenosine deaminase activity in patients with systemic lupus erythematosus: a study based on ADA1 and ADA2 isoenzymes pattern

et al. 2011

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Adenosine deaminase (ADA) plays a crucial role in the development and maintenance of normal immune system. So, any immunological imbalances could associate with its altered activity in serum. This study evaluated the activity of total ADA and its isoenzymes in serum of 45 patients with systemic lupus erythematosus (SLE). Included were 23 patients with active SLE, 22 during the inactive phase of the disease, and 45 healthy subjects. Our results provided evidence that the significantly elevated total ADA activity in serum of SLE patients is correlated mainly with the increased ADA2 level. The highest mean ADA2 activity during the relapse phase of the disease could be an indication to the macrophages, the main source of ADA2. It might be concluded that ADA and its isoenzymes analysis in serum of patients could be used as a useful and non-invasive diagnostic tool in evaluation of SLE active phase and the disease severity.

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Section: Introductionmentioning

confidence: 99%

Serum adenosine deaminase activity in patients with systemic lupus erythematosus: a study based on ADA1 and ADA2 isoenzymes pattern

et al. 2011

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Differential deoxyadenosine toxicity to immature rabbit cartilage in vitro. a model for the chondro‐osseous dysplasia of adenosine deaminase deficiency

Wortmann

Veum

Ryan

et al. 1989

Arthritis & Rheumatism

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Deoxyadenosine metabolism was investigated in rabbit growth plate and articular cartilage to elucidate the biochemical basis for the chondro-osseous dysplasia observed in adenosine deaminase (ADA) deficiency. Models of ADA deficiency, the combination of deoxyadenosine and either of 2 ADA inhibitors, were selectively toxic to immature cartilage, supporting the hypothesis that the chondro-osseous dysplasia of ADA deficiency is the consequence of the enzyme deficiency. Depletion of ATP may play a role in the altered chondrocyte viability and function observed in this model.Adenosine deaminase (ADA) (EC 3.5.4.4) catalyzes the irreversible deamination of adenosine and deoxyadenosine to inosine and deoxyinosine, respectively. An inherited deficiency of ADA causes an autosomal recessive form of severe combined immunodeficiency disease (1-3). Clinically, ADA-deficient individuals suffer from overwhelming infection and malabsorption. In addition to immune dysfunction, ADA-deficient individuals develop abnormalities in bone and cartilage, termed chondro-osseous dysplasia ( 4 6 ) , which is recognized by characteristic radiographic changes and is associated with a distinctive histopathologic pattern. Although the radiographic changes are not entirely specific, they are quite prevalent in chondro-osseous dysplasia and improve with successful enzyme replacement therapy (7,s).The absence of ADA activity results in the predictable increased concentrations of deoxyadenosine and adenosine in deficient individuals (9,lO). In vivo, the accumulation of deoxyadenosine leads to increased concentrations of deoxyATP in erythrocytes, peripheral blood lymphocytes, and bone marrow cells (10,ll). Precisely how the accumulation of these metabolites causes immune dysfunction is uncertain. Possibilities include inhibition of ribonucleotide reductase (EC 1.17.4.1) by deoxyATP (10,l I), inhibition and inactivation of S-adenosyl-L-homocysteine (SAH) hydrolase (EC 3.3.1.1) by adenosine and deoxyadenosine (12,131, and ATP depletion (1416). Also, deoxyadenosine and its metabolites have been observed to cause accumulation of DNA strand breaks (17,18), inhibit RNA synthesis (18,19), lower NAD pools (lS), and inhibit methionine synthesis (20).The metabolic abnormalities that cause the chondro-osseous dysplasia are also not understood. We have investigated the effects of ADA inhibition in vitro on chondrocyte viability and function. Our results support the hypothesis that the chondro-osseous dysplasia observed in ADA deficiency is the consequence of the disordered purine metabolism that results when ADA activity is absent, and suggest that ATP depletion may play a significant role in the pathogenesis of the cartilage and bone pathology observed.

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Chemistry and Biological Profile of Immunosuppressants

Shen

1985

Pharmacology

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Suppression of human lymphocyte DNA and protein synthesis in vitro by adenosine and eight modified adenine nucleosides in the presence or in the absence of adenosine deaminase inhibitors, 2′-deoxycoformycin (DCF) and erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA)

Cited by 7 publications

References 25 publications

Serum adenosine deaminase activity in patients with systemic lupus erythematosus: a study based on ADA1 and ADA2 isoenzymes pattern

Serum adenosine deaminase activity in patients with systemic lupus erythematosus: a study based on ADA1 and ADA2 isoenzymes pattern

Differential deoxyadenosine toxicity to immature rabbit cartilage in vitro. a model for the chondro‐osseous dysplasia of adenosine deaminase deficiency

Chemistry and Biological Profile of Immunosuppressants

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