Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the expression of mRNA encoding adenosine deaminase (ADA; EC 3.5.4.4), purine nucleoside phosphorylase (PNP; EC 2.4.2.1), and terminal deoxynucleotidyltransferase (TdT; EC 2.7.7.31) in different leukemic cell lines of B- and T-cell lineage. Incubation of leukemic cells in the presence of the phorbol esters, 12-O-tetradecanoyl-phorbol-13-acetate or phorbol 12,13-dibutyrate, resulted in reduction of ADA and TdT mRNA levels, while PNP mRNA levels increased under the same treatment. The effect of TPA on the activity of these enzymes correlated well with its effects on their mRNA levels. TPA caused a 40% decrease in ADA and a 60% decrease in TdT enzyme activity, after 6 h of treatment. In contrast, PNP activity increased up to 200% after 12 h of incubation with the phorbol ester. The changes induced by the phorbol esters in the levels of mRNA of ADA, PNP, and TdT, and their enzyme activities in human leukemic cell lines mimic the changes in the activities of these enzymes in developing T-lymphocytes during differentiation in vivo, suggesting a role for protein kinase C in the regulation of ADA, PNP, and TdT gene expression during lymphoid cell differentiation.
 ...
PMID:Phorbol esters induce changes in adenosine deaminase, purine nucleoside phosphorylase, and terminal deoxynucleotidyl transferase messenger RNA levels in human leukemic cell lines. 211 May 2

After four days of treatment with 10(-8) M TPA, differentiation of the human T-lymphoblastoid cell line MOLT-4 was induced along the T cell lineage, confirmed by a fall in adenosine deaminase and 5'-ectonucleotidase and a rise in purine nucleoside phosphorylase activity. TPA-treated cells became resistant to the cytotoxic effects of 1-beta-D-arabinofuranosylcytosine (Ara-C), 9-beta-D-arabinofuranosyladenine (Ara-A), and 2-chlorodeoxyadenosine. This was, in part, due to the altered cell cycle distribution (accumulation of cells in the G1 phase), since the toxicity of Ara-C and Ara-A is S phase specific. The diminished rate of Ara-C transport concomitant with Ara-CTP formation after TPA treatment is considered to be the biochemical basis for this acquired resistance.
 ...
PMID:Changes in sensitivity to anticancer drugs during TPA-induced cellular differentiation in a human T-lymphoblastoid cell line (MOLT-4). 326 Jun 48

The expression of the enzyme adenosine deaminase (ADA) decreases in the course of the differentiation of the human promyelocytic leukemic cell line HL-60, dependent on the pathway chosen. Differentiation to monocytes as induced by the phorbol ester TPA leads to a 50% reduction of enzyme activity. Induction to myeloid cells as induced by DMSO has a slower and less extensive (75% remaining activity) effect. The reduction in ADA enzymatic activity is preceded by a 5-10 fold reduction in ADA-specific mRNA which is also more rapid during TPA-induced differentiation. In contrast, c-myc mRNA expression is both in TPA- and DMSO-induced differentiation reduced to less then 5% of its initial level within 4h. Nuclear run-on analysis revealed that the reduction of c-myc-mRNA expression during both TPA- and DMSO-induced differentiation could be ascribed to the abolition of transcription of the third exon, whereas no change in the transcription of the first exon could be observed. No change could be detected in the rate of transcription of either the 5' and 3' parts of the ADA gene during TPA- and DMSO-induced differentiation, indicating that the expression of the ADA gene in HL-60 is controlled at a posttranscriptional level.
 ...
PMID:Adenosine deaminase mRNA expression is regulated posttranscriptionally during differentiation of HL-60 cells. 330 3

Previous studies have shown that thymosin (fraction 5) is able to induce surface differentiation markers on normal murine bone marrow T-cell precursors. Phorbol ester (TPA) promotes differentiation of human leukaemic lymphoblasts as assessed by changes in phenotypic surface markers and terminal deoxynucleotidyl transferase (TdT) activity. Changes in levels of purine degradative enzymes occur during T-cell maturation with a fall in adenosine deaminase (ADA) and a rise in purine nucleoside phosphorylase (PNP) and 5'nucleotidase (5'NT) activities. We have now investigated the effect of both thymosin (fraction 5) and TPA on a human leukaemic T-cell line (MOLT-3) in expression of the surface antigenic markers NAI/34 (a marker of immature thymocytes) and OKT11 (which corresponds to the sheep erythrocyte receptor) and of TdT, ADA, PNP and 5'NT. Thymosin (after 96 h incubation) significantly reduced the number of cells positive for NAI/34 from 76.0 +/- 5.0% (mean +/- S.D.) to 51.3 +/- 9.3% (p less than 0.01) but caused no significant change in the percentage of TdT or OKT11 positive cells. ADA levels were significantly reduced (p less than 0.02) and 5'NT levels were significantly elevated (mean increase 303 +/- 142% of control, p less than 0.001) but the increase in PNP level (108 +/- 16.8% of control) was not significant (p greater than 0.05). On the other hand, TPA (after 96 h incubation) significantly reduced cells positive for NAI/34 from 76.0 +/- 5.0 to 30.0 +/- 9.8% and for TdT from 81.7 +/- 6.5 to 17.3 +/- 4.4% and increased OKT11 positive cells from 67.3 +/- 5.5 to 89.0 +/- 2.8% (p less than 0.001). TPA caused no significant change in 5'NT or ADA levels (p greater than 0.05), but an increase in PNP level to 158 +/- 12.9% of control (p less than 0.02). The present study demonstrates for the first time that the normal thymic hormone, thymosin is capable of inducing differentiation changes in thymic derived human leukaemic cells. In addition, it shows that different inducing agents may cause different patterns of differentiation changes in leukaemic cells.
 ...
PMID:Effect of thymosin and phorbol ester on purine metabolic enzymes and cell surface phenotype in a malignant T-cell line (MOLT-3). 631 30